Antibacterial agents

ABSTRACT

Antibacterial compounds of formula I are provided:  
                 
As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

This application claims benefit of priority to the following U.S.Provisional Patent Applications, Ser. No. 60/438,523, filed Jan. 8,2003; Ser. No. 60/466,974, filed Apr. 30, 2003; and Ser. No. 60/520,211filed Nov. 13, 2003; each of which is incorporated herein by referencein its entirety for any purpose.

FIELD OF THE INVENTION

This invention pertains generally to treating infections caused bygram-negative bacteria. More specifically, the invention describedherein pertains to treating gram-negative infections by inhibitingactivity of UDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosaminedeacetylase (LpxC). The present invention provides small moleculeinhibitors of LpxC, pharmaceutical formulations containing suchinhibitors, methods of treating patients with such pharmaceuticalformulations, and to methods of preparing such pharmaceuticalformulations and inhibitors. The inhibitors can be used to treatGram-negative infections of patients alone and in combination with otherantibacterials.

BACKGROUND OF THE INVENTION

Over the past several decades, the frequency of antimicrobial resistanceand its association with serious infectious diseases have increased atalarming rates. The increasing prevalence of resistance among nosocomialpathogens is particularly disconcerting. Of the over 2 millionnosocomial infections occurring each year in the United States, 50 to60% are caused by antimicrobial-resistant strains of bacteria. This highrate of resistance increases the morbidity, mortality, and costsassociated with nosocomial infections. In the United States, nosocomialinfections are thought to contribute to or cause more than 77,000 deathsper year and cost approximately $5 to $10 billion annually. AmongGram-positive organisms, the most important resistant pathogens aremethicillin- (oxacillin-) resistant Staphylococcus aureus,β-lactam-resistant and multidrug-resistant pneumococci, andvancomycin-resistant enterococci. Important causes of Gram-negativeresistance include extended-spectrum β-lactamases (ESBLs) in Klebsiellapneumoniae, Escherichia coli, and Proteus mirabilis, high-levelthird-generation cephalosporin (Amp C) β-lactamase resistance amongEnterobacter species and Citrobacter freundii, and multidrug-resistancegenes observed in Pseudomonas aeruginosa, Acinetobacter, andStenotrophomonas maltophilia. (Jones R N 2001 Chest 119 (supplement),397S-404S: Resistance patterns among nosocomial pathogens: Trends overthe past few years.)

The problem of antibacterial resistance is compounded by the existenceof bacterial strains resistant to multiple antibacterials. For example,Pseudomonas aeruginosa isolates resistant to fluoroquinolones arevirtually all resistant to additional antibacterials (Sahm D F et al2001 Antimicrobial Agents and Chemotherapy 45, 267-274: Evaluation ofcurrent activities of fluoroquinolones against gram-negative bacilliusing centralized in vitro testing and electronic surveillance.)

Thus there is a need for new antibacterials, particularly antibacterialswith novel mechanisms of action. Most of the antibacterial discoveryeffort in the pharmaceutical industry is aimed at development of drugseffective against gram-positive bacteria. However, there is also a needfor new gram-negative antibacterials. Gram-negative bacteria are ingeneral more resistant to a large number of antibacterials andchemotherapeutic agents than are gram-positive bacteria. A survey ofrecently reported antibacterials of natural origin showed that over 90%lacked activity against Escherichia coli, although they were activeagainst gram-positive bacteria. The outer membrane of gram-negativebacteria contributes to this intrinsic resistance by acting as anefficient permeability barrier, because the narrow porin channels limitthe penetration of hydrophilic solutes and the low fluidity of thelipopolysaccharide leaflet slows down the inward diffusion of lipophilicsolutes. A second mechanism contributes to the intrinsic resistance ofgram-negative bacteria. Recent studies showed that multiple drug effluxpumps, sometimes with unusually broad specificity, act as this secondfactor to create the general intrinsic resistance of gram-negativebacteria. When their expression levels are elevated as a consequence ofphysiological regulation or genetic alteration, they can frequentlyproduce impressive levels of resistance to a wide variety ofantimicrobial agents. (Nikaido H 1998 Clinical Infectious Diseases27(Suppl 1), S3241: Antibacterial resistance caused by gram-negativemultidrug efflux pumps.)

Historically, most development of antimicrobial agents has beenrelatively empirical. Active compounds have generally been found viascreening soil, sewage, water, and other natural substances to detectantimicrobial-producing organisms, or by screening various chemicalcompounds. Once a leading candidate has been found and its chemicalstructure determined, a series of analogs is made to identify an optimalcompound for further clinical development. A more rational approachinvolves the defining (if new targets, such as genes or enzymaticfunctions, responsible for a crucial cellular essential activity. Oncethis has been done, inhibitors or blockers of the function or geneproduct can be developed.

In order to identify potential targets for novel gram-negativeantibacterial agents, studies aimed at identifying all essential andimportant genes in Pseudomonas aeruginosa have been performed. Among theessential genes identified was lpxC, that encodes the enzymeuridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine deacetylase(LpxC). This enzyme is the first committed step in the synthesis oflipid A, the lipid moiety of lipopolysaccharide, that is an essentialcomponent of all gram-negative bacteria. It therefore is an attractivetarget for novel antibacterials. In order to be useful as antibacterialagents, LpxC inhibitors would not only have to inhibit the enzymaticactivity of LpxC from a variety of bacteria, but would have to defeatthe intrinsic resistance mechanisms of gram-negative bacteria, asdescribed above: they would have to penetrate the outer membrane and berelatively unsusceptible to multidrug efflux pumps.

Researchers have identified a few compounds with antibacterial activitythat target lipid A biosynthesis. WO 97/42179 to Patchett et al.discloses compounds of the formula:

The compounds possess activity against certain gram-negative organisms,for example Escherichia coli, but are not active against other medicallyimportant gram-negative bacteria, for example Pseudomonas aeruginosa.Subsequent studies have found that the primary reason for theirinactivity against particular, medically important gram-negativebacteria is their poor ability to inhibit P. aeruginosa LpxC; efflux bythe major multidrug efflux pump or inability to penetrate the outermembrane were not the critical factors.

Jackman et al., in J. Biol. Chem. (vol. 275, no. 15, Apr. 14, 2000, pps.11002-11009), discuss the mechanism of lipid A biosynthesis in thecontext of gram-negative bacteria and discloses a new class ofhydroxamate-containing inhibitors of LpxC. Wyckoff et al., in Trends inMicrobiology (vol. 6, no. 4, April 1998, pps. 154-159), discuss the roleof LpxC in lipid A biosynthesis and its role in regulation. Wyckoff etal. disclose a few oxazoline hydroxamic acids that inhibit bacterialgrowth. However, Wyckoff et al. also discuss the shortcomings of theavailable deacetylase inhibitors as bactericidal agents againstPseudomonas and that more work is needed to be done in the area.

Thus, an increasing need exists for LpxC inhibitors that have activityas bactericidal agents against gram-negative bacteria. It is,accordingly, an object of this invention to provide compounds andcombinations of such compounds for use in the preparation ofantibacterials and other pharmaceuticals capable of inhibitingGram-negative bacterial infections.

U.S. Patent Publication No. 2001/0053555 (U.S. patent application Ser.No. 08/958,638) published Dec. 20, 2001, corresponding to WO 98/18754published May 7, 1998 discloses a combinatorial library ofhydroxylamine, hydroxamic acid, hydroxyurea and hydroxylsulfonamidecompounds purported to be potentially useful as inhibitors ofmetalloproteases. U.S. Pat. No. 6,281,245, a continuation in part ofU.S. Ser. No. 08/958,638 claims a method of inhibiting a deformylaseenzyme by administering one of the hydroxylamine compounds from thecombinatorial library as disclosed in U.S. Patent Publication No.2001/0053555 and the corresponding WO 98/18754. Related to the abovedisclosed patent publications is WO 99/57097, published Nov. 11, 1999,that discloses a method of solid phase synthesis of the hydroxylaminelibrary of compounds. WO 00/61134 (to British Biotech PharmaceuticalsLimited), published Oct. 19, 2000, discloses compounds of the formulabelow:

The compounds are useful as antimicrobial agents that are believed tohave bactericidal activity at least in part to intracellular inhibitionof bacterial polypeptide deformylase.

In an earlier to British Biotech Pharmaceuticals Limited, WO 99/39704,published Aug. 12, 1999, compounds of the formula below are disclosed:

The compounds are useful as antimicrobial agents useful againstgram-negative and gram positive bacteria.

Recently, De Novo Pharmaceuticals LTD disclosed in WO 02/50081,published Jun. 27, 2002, antibacterial and antiprotozoal agents havingthe formulae shown below:

The patent publication discusses that the antibacterial activity is due,at least in part, to intracellular inhibition of bacterial polypeptidedeformylase.

SUMMARY OF THE INVENTION

The present invention provides novel compounds, pharmaceuticalformulations including the compounds, methods of inhibitingUDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC),and methods of treating gram-negative bacterial infections.In one embodiment, the present invention provides compounds of formulaI:

or stereoisomers, pharmaceutically acceptable salts, esters, andprodrugs thereof, whereinE is absent or selected from the group consisting of

-   -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted C₂-C₆-alkenyl,    -   (4) substituted or unsubstituted C₂-C₆-alkynyl,    -   (5) substituted or unsubstituted aryl,    -   (6) substituted or unsubstituted heterocyclyl, and    -   (7) substituted or unsubstituted heteroaryl;        L is absent or selected from the group consisting of    -   (1) substituted or unsubstituted C₁-C₆-alkyl,    -   (2) —(NH)₀₋₁—C(R^(1L),R^(2L))—NR^(3L)—C(R^(1L),R^(2L))—,    -   (3) —(NH)₀₋₁—(R^(1L),R^(2L))—O—C(R^(1L),R^(2L)),    -   (4) —C(R^(1L),R^(2L))—O—C(R^(1L),R^(2L))—,    -   (5) —(CH₂)_(j)—NR^(3L)—C(R^(1L),R^(2L))—CONH—(CH₂)_(k)—,    -   (6) —CO—C(R^(1L),R^(2L))—NHCO—,    -   (7) —CONH—,    -   (8) —NHCO—,    -   wherein    -   R^(1L), R^(2L), and R^(3L) are independently selected from the        group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) C₁-C₆-alkyl substituted with aryl,        -   (d) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (e) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S;    -   j is an integer of 0-4;    -   k is an integer of 0-4;        D is absent or selected from the group consisting of    -   (1) substituted or unsubstituted C₃-C₈-cycloalkyl,    -   (2) substituted or unsubstituted aryl,    -   (3) substituted or unsubstituted heterocyclyl, and    -   (4) substituted or unsubstituted heteroaryl;        G is absent or selected from the group consisting of    -   (1) —(CH₂)_(i)—O—(CH₂)_(i)—,    -   (2) —(CH₂)_(i)—S—(CH₂)_(i)—,    -   (3) —(CH₂)_(i)—NR^(g)—(CH₂)_(i)—,    -   (4) —C(═O)—,    -   (5) —NHC(═O)—,    -   (6) —C(═O)NH—,    -   (7) —(CH₂)_(i)NHCH₂C(═O)NH—,    -   (8) —C≡C—,    -   (9) —C≡C—C≡C—, and    -   (10) —C═C—;    -   wherein    -   Rg is H or substituted or unsubstituted C₁-C₆-alkyl;    -   i is an interger of 0-4;        Y is selected from the group consisting of    -   (1) substituted or unsubstituted C₃-C₈-cycloalkyl,    -   (2) substituted or unsubstituted aryl,    -   (3) substituted or unsubstituted heterocyclyl, and    -   (4) substituted or unsubstituted heteroaryl;        X is selected from the group consisting of    -   (1) —(C═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)C—,    -   (3) —C₂-C₆-alkenyl-(C═O)—,    -   (4) —C₂-C₆-alkynyl-(C═O)—, and    -   (5) —CH₂—;    -   or when B is absent, X and A, together with the atoms to which        they are attached can form a heterocyclic ring, having from 5 to        8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring        system are selected from N, O and S;        B is a absent or    -   wherein R^(1b) and R^(2b), are independently selected from the        group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) substituted or unsubstituted C₂-C₆-alkenyl,        -   (d) substituted or unsubstituted C₂-C₆-alkynyl,        -   (e) substituted or unsubstituted aryl,        -   (f) substituted or unsubstituted heterocyclyl,        -   (g) substituted or unsubstituted heteroaryl,        -   (h) C₁-C₆-alkyl substituted with aryl,        -   (i) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (j) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1b) and R^(2b), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S;    -   q is an integer of 0-4;        R₃ is H or substituted or unsubstituted C₁-C₆-alkyl,    -   or R₃ and A, together with the atoms to which they are attached        can form a substituted or unsubstituted 3-10 membered cycloalkyl        or a heterocyclic ring system, wherein the heterocyclic ring        system may have from 3 to 10 ring atoms, with 1 to 2 rings being        in the ring system and contain from 1-4 heteroatoms selected        from N, O and S;        R⁴ is H or substituted or unsubstituted C₁-C₆-alkyl,    -   or R₄ and A, together with the atoms to which they are attached        can form a substituted or unsubstituted heterocyclic ring,        having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the        heterocyclic ring system are selected from N, O and S;        n is an integer of 0-6;        A is selected from the group consisting of    -   (1) H,    -   (2) —(CH₂)_(r)C(R^(1a),R^(2a))(CH₂)_(s)OR^(3a),    -   (3) —(CH₂)_(r)C(R^(1a),R^(2a))N(R^(4a),R^(5a)),    -   (4) —(CH₂)_(r)C(R^(1a),R^(2a))N(R^(4a))COR^(3a),    -   (5) —(CH₂)_(r)C(R^(1a),R^(2a))NHCON(R^(4a),R^(5a)),    -   (6) —(CH₂)_(r)C(R^(1a),R^(2a))NHC(═NH)N(R^(4a),R^(5a)),    -   (7) —CH(R^(1a),R^(2a)),    -   (8) —C≡CH,    -   (9) —(CH₂)_(r)C(R^(1a),R^(2a))CN,    -   (10) —(CH₂)_(r)C(R^(1a),R^(2a))CO₂R^(3a), and    -   (11) —(CH₂)_(r)C(R^(1a),R^(2a))CON(R^(4a),R^(5a)),    -   wherein R^(1a), R^(2a), R^(3a), R^(4a), and R^(5a) are        independently selected from the group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) substituted or unsubstituted aryl,        -   (d) substituted or unsubstituted heterocyclyl,        -   (e) substituted or unsubstituted heteroaryl,        -   (f) C₁-C₆-alkyl substituted with aryl,        -   (g) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (h) C₁-C₆-alkyl substituted with heteroaryl,        -   or R^(4a) and R^(5a) together with the N atom to which they            are attached can form a substituted or unsubstituted            heterocyclic ring, having from 5 to 8 ring atoms, wherein            1-2 ring atoms of the heterocyclic ring system are selected            from N, O and S;    -   r is an integer of 0-4;    -   s is an integer of 0-4;        Q is absent or selected from the group consisting of    -   (1) —C(═O)N(R₁,R₂);    -   (2) —NHC(═O)N(R₁,R₂),    -   (3) —N(OH)C(═O)N(R₁,R₂),    -   (4) —CH(OH)C(═O)N(R₁,R₂),    -   (5) —CH[N(R^(2q),R^(3q))]C(═O)N(R₁,R₂),    -   (6) —CHR^(1q)C(═O)N(R₁,R₂),    -   (7) —CO₂H,    -   (8) —C(═O)NHSO₂R^(4q),    -   (9) —SO₂NH₂,    -   (10) —N(OH)C(═O)R^(1q),    -   (11) —N(OH)SO₂R^(4q),    -   (12) —NHSO₂R^(4q),    -   (13) —SH,    -   (14) —CH(SH)(CH₂)₀₋₁C(═O)N(R₁,R₂),    -   (15) —CH(SH)(CH₂)₀₋₁CO₂H,    -   (16) —CH(OH)(CH₂)₀₋₁CO₂H,    -   (17) —CH(SH)CH₂CO₂R^(1q),    -   (18) —CH(OH)(CH₂)SO₂NH₂,    -   (19) —CH(CH₂SH)NHCOR^(1q),    -   (20) —H(CH₂SH)NHSO₂R^(4q),    -   (21) —CH(CH₂SR^(5q))CO₂H,    -   (22) —CH(CH₂SH)NHSO₂NH₂,    -   (23) —CH(CH₂OH)CO₂H,    -   (24) —H(CH₂OH)NHSO₂NH₂,    -   (25) —C(═O)CH₂CO₂H,    -   (26) —C(═O)(CH₂)₀₋₁CONH₂,    -   (27) —OSO₂NHR^(5q),    -   (28) —SO₂NHNH₂,    -   (29) —P(═O)(OH)₂,    -   (30)    -   (31)    -   (32)    -   wherein    -   R₁ is selected from the group consisting of        -   (1) H,        -   (2) —OH,        -   (3) —OC₁₋₆-alkyl,        -   (4) —N(R^(2q),R^(3q)), and        -   (5) substituted or unsubstituted C₁₋₆-alkyl;    -   R₂ is selected from the group consisting of        -   (1) H,        -   (2) substituted or unsubstituted C₁-C₆-alkyl,        -   (3) substituted or unsubstituted C₂-C₆-alkenyl,        -   (4) substituted or unsubstituted C₂-C₆-alkenyl,        -   (5) substituted or unsubstituted aryl,        -   (6) substituted or unsubstituted heterocyclyl,        -   (7) substituted or unsubstituted heteroaryl,        -   (8) C₁-C₆-alkyl substituted with aryl,        -   (9) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (10) C₁-C₆-alkyl substituted with heteroaryl,        -   or R¹ and R², together with the N atom to which they are            attached can form a substituted or unsubstituted            heterocyclic ring, having from 3 to 10 ring atoms, wherein            1-4 ring atoms of the heterocyclic ring system are selected            from N, O and S,        -   or R² and R⁴, together with the N atoms to which they are            attached can form a substituted or unsubstituted            heterocyclic ring, having from 3 to 10 ring atoms, wherein            1-4 ring atoms of the heterocyclic ring system are selected            from N, O and S;    -   R^(1q), R^(2q), R^(3q), R^(4q), and R^(5q) are selected from H        or C₁-C₆ alkyl,        wherein B is absent, or E, 1, G, and B are absent, or E, L, and        G are absent, or E, L, and B are absent, or E, L, D, G, and B        are absent.

In one aspect, the invention provides a method of inhibiting adeacetylase enzyme in a gram-negative bacteria, thereby affectingbacterial growth, comprising administering to a patient in need of suchinhibition a compound of formula I.

In another aspect, the invention provides a method of inhibiting LpxC,thereby modulating the virulence of a bacterial infection, comprisingadministering to a patient in need of such inhibition a compound offormula I.

In another aspect, the invention provides a method for treating asubject with a gram-negative bacterial infection comprisingadministering to the subject in need thereof an antibacteriallyeffective amount of a compound of formula I with a pharmaceuticallyacceptable carrier. In a preferred embodiment of the method oftreatment, the subject is a mammal and in some embodiments, a human.

In another aspect, the invention provides a method of administering aninhibitory amount of a compound of formula I to fermentative ornon-fermentative gram-negative bacteria. In a preferred embodiment ofthe method of administering an inhibitory amount of a compound offormula I to fermentative or non-fermentative gram-negative bacteria,the gram-negative bacteria are selected from the group consisting ofPseudomonas aeruginosa, Stenotrophomonas maltophila, Burkholderiacepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae,Haemophilus, and Neisseria species.

In another embodiment, the invention provides a method of administeringan inhibitory amount of a compound of formula I to gram-negativebacteria, such as Enterobacteriaceae which is selected from the groupconsisting of organisms such as Serratia, Proteus, Klebsiella,Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea,and Edwardsiella species and Escherichia coli.

Another embodiment of the invention provides a pharmaceuticalcomposition comprising an effective amount of a compound of Formula Iwith a pharmaceutically acceptable carrier thereof.

Pharmaceutical formulations according to the present invention areprovided which include any of the compounds described above incombination with a pharmaceutically acceptable carrier.

Another embodiment of the invention provides a method ofco-administering the compound of formula I with other therapeutic agentsthat are selected for their particular usefulness against the conditionthat is being treated.

For example, the compound of formula I is useful in combination withother anti-bacterial agents. The compound of formula I augments thesensitivity of gram-negative bacteria to existing classes ofantibacterials. Combinations of the presently disclosed compounds withother anti-bacterial agents are within the scope of the invention. Suchanti-bacterial agents include, but are not limited to, erythromycin,rifampicin, Nalidixic acid, carbenicillin, bacitracin, cycloserine,fosfomycin, and vancomycin.

DETAILED DESCRIPTION

The present invention provides novel, compounds, methods for inhibitingLpxC in gram-negative bacteria, and novel methods for treating bacterialinfections. The compounds provided herein can be formulated intopharmaceutical formulations and medicaments that are useful in themethods of the invention. The invention also provides for the use of thecompounds in preparing medicaments and pharmaceutical formulations, foruse of the compounds in inhibiting LpxC, and for use of the compounds intreating bacterial infections in a subject

The following abbreviations and definitions are used throughout thisapplication:

“LpxC” is an abbreviation that stands forUDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase.

Generally, reference to a certain element such as hydrogen or H is meantto include all isotopes of that element. For example, if an R group isdefined to include hydrogen or H, it also includes deuterium andtritium.

The phrase “alkyl” refers to alkyl groups that do not containheteroatoms. Thus the phrase includes straight chain alkyl groups suchas methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl and the like. The phrase also includes branchedchain isomers of straight chain alkyl groups, including but not limitedto, the following that are provided by way of example: —CH(CH₃)₂,—CH(CH₃)(CH₂CH₃), —CH(CH₂CH₃)₂, —C(CH₃)₃, —C(CH₂CH₃)₃, —CH₂CH(CH₃)₂,—CH₂CH(CH₃)(CH₂CH₃), —CH₂CH(CH₂CH₃)₂, —CH₂C(CH₃)₃, —CH₂C(CH₂CH₃)₃,—CH(CH₃)CH(CH₃)(CH₂CH₃), —CH₂CH₂CH(CH₃)₂, —CH₂CH₂CH(CH₃)(CH₂CH₃),—CH₂CH₂CH(CH₂CH₃)₂, —CH₂CH₂C(CH₃)₃, —CH₂CH₂C(CH₂CH₃)₃,—CH(CH₃)CH₂CH(CH₃)₂, —CH(CH₃)CH(CH₃)CH(CH₃)₂,—CH(CH₂CH₃)CH(CH₃)CH(CH₃)(CH₂CH₃), and others. The phrase also includescyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, and cyclooctyl and such rings substituted withstraight and branched chain alkyl groups as defined above. Thus thephrase alkyl groups includes primary alkyl groups, secondary alkylgroups, and tertiary alkyl groups. Preferred alkyl groups includestraight and branched chain alkyl groups and cyclic alkyl groups having1 to 12 carbon atoms.

The phrase “substituted alkyl” refers to an alkyl group as defined abovein which one or more bonds to a carbon(s) or hydrogen(s) are replaced bya bond to non-hydrogen and non-carbon atoms such as, but not limited to,a halogen atom such as F, Cl, Br, and I; an oxygen atom in groups suchas hydroxyl groups, alkoxy groups, aryloxy groups, and ester groups; asulfur atom in groups such as thiol groups, alkyl and aryl sulfidegroups, sulfone groups, sulfonyl groups, and sulfoxide groups; anitrogen atom in groups such as amines, amides, alkylamines,dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides,imides, and enamines; a silicon atom in groups such as in trialkylsilylgroups, dialkylarylsilyl groups, alkyldiarylsilyl groups, andtriarylsilyl groups; and other heteroatoms in various other groups.Substituted alkyl groups also include groups in which one or more bondsto a carbon(s) or hydrogen(s) atom is replaced by a higher-order bond(e.g., a double- or triple-bond) to a heteroatom such as oxygen in oxo,carbonyl, carboxyl, and ester groups; nitrogen in groups such as imines,oximes, hydrazones, and nitriles. Substituted alkyl groups furtherinclude alkyl groups in which one or more bonds to a carbon(s) orhydrogen(s) atoms is replaced by a bond to an aryl, heterocyclyl group,or cycloalkyl group. Preferred substituted alkyl groups include, amongothers, alkyl groups in which one or more bonds to a carbon or hydrogenatom is/are replaced by one or more bonds to fluorine atoms. Anotherpreferred substituted alkyl group is the trifluoromethyl group and otheralkyl groups that contain the trifluoromethyl group. Other preferredsubstituted alkyl groups include those in which one or more bonds to acarbon or hydrogen atom is replaced by a bond to an oxygen atom suchthat the substituted alkyl group contains a hydroxyl, alkoxy, or aryloxygroup. Still other preferred substituted alkyl groups include alkylgroups that have an amine, or a substituted or unsubstituted alkylamine,dialkylamine, arylamine, (alkyl)(aryl)amine, diarylamine,heterocyclylamine, diheterocyclylamine, (alkyl)(heterocyclyl)amine, or(aryl)(heterocyclyl)amine group.

The phrase “alkenyl” refers to straight and branched chain and cyclicgroups such as those described with respect to alkyl groups as definedabove, except that at least one double-bond exists between two carbonatoms. Examples include, but are not limited to vinyl, —CH═C(H)(CH₃),—CH═C(CH₃)₂, —C(CH₃)—(H)₂, —C(CH₃)═C(H)(CH₃), —C(CH₂CH₃)═CH₂,cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl,and hexadienyl among others. The phrase “substituted alkenyl” has thesame meaning with respect to alkenyl groups that substituted alkylgroups had with respect to unsubstituted alkyl groups. A substitutedalkenyl group includes alkenyl groups in which a non-carbon ornon-hydrogen atom is bonded to a carbon double bonded to another carbonand those in which one of the non-carbon or non-hydrogen atoms is bondedto a carbon not involved in a double bond to another carbon.

The phrase “alkynyl” refers to straight and branched chain groups suchas those described with respect to alkyl groups as defined above, exceptthat at least one triple bond exists between two carbon atoms. Examplesinclude, but are not limited to —C≡C(H), —C≡C(CH₃), —C≡C(CH₂CH₃),—C(H₂)C≡C(H), —C(H)₂C≡(CH₃), and —C(H)₂C≡C(CH₂CH₃) among others. Thephrase “substituted alkynyl” has the same meaning with respect toalkynyl groups that substituted alkyl groups had with respect tounsubstituted alkyl groups. A substituted alkynyl group includes alkynylgroups in which a non-carbon or non-hydrogen atom is bonded to a carbontriple bonded to another carbon and those in which a noncarbon ornon-hydrogen atom is bonded to a carbon not involved in a triple bond toanother carbon.

The phrase “heterocyclyl” refers to both aromatic and nonaromatic ringcompounds including monocyclic, bicyclic, and polycyclic ring compoundssuch as, but not limited to, quinuclidinyl, containing 3 or more ringmembers of which one or more is a heteroatom such as, but not limitedto, N, O, and S. Although the phrase “unsubstituted heterocyclyl”includes condensed heterocyclic rings such as benzimidazolyl, it doesnot include heterocyclyl groups that have other groups such as alkyl orhalo groups bonded to one of the ring members as compounds such as2-methylbenzimidazolyl are substituted heterocyclyl groups. Examples ofheterocyclyl groups include, but are not limited to: unsaturated 3 to 8membered rings containing 1 to 4 nitrogen atoms such as, but not limitedto pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl,pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g. 4H-1,2,4-triazolyl,1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl etc.), tetrazolyl, (e.g.1H-tetrazolyl, 2H tetrazolyl, etc.); saturated 3 to 8 membered ringscontaining 1 to 4 nitrogen atoms such as, but not limited to,pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl; condensedunsaturated heterocyclic groups containing 1 to 4 nitrogen atoms suchas, but not limited to, indolyl, isoindolyl, indolinyl, indolizinyl,benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl;unsaturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1to 3 nitrogen atoms such as, but not limited to, oxazolyl, isoxazolyl,oxadiazolyl (e.g. 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,5-oxadiazolyl, etc.); saturated 3 to 8 membered rings containing 1to 2 oxygen atoms and 1 to 3 nitrogen atoms such as, but not limited to,morpholinyl; unsaturated condensed heterocyclic groups containing 1 to 2oxygen atoms and 1 to 3 nitrogen atoms, for example, benzoxazolyl,benzoxadiazolyl, benzoxazinyl (e.g. 2H-1,4-benzoxazinyl etc.);unsaturated 3 to 8 membered rings containing 1 to 3 sulfur atoms and 1to 3 nitrogen atoms such as, but not limited to, thiazolyl,isothiazolyl, thiadiazolyl (e.g. 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.); saturated 3 to 8 memberedrings containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms such as,but not limited to, thiazolodinyl; saturated and unsaturated 3 to 8membered rings containing 1 to 2 sulfur atoms such as, but not limitedto, thienyl, dihydrodithiinyl, dihydrodithionyl, tetrahydrothiophene,tetrahydrothiopyran; unsaturated condensed heterocyclic rings containing1 to 2 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limitedto, benzothiazolyl, benzothiadiazolyl, benzothiazinyl (e.g.2H-1,4-benzothiazinyl, etc.), dihydrobenzothiazinyl (e.g.2H-3,4-dihydrobenzothiazinyl, etc.), unsaturated 3 to 8 membered ringscontaining oxygen atoms such as, but not limited to furyl; unsaturatedcondensed heterocyclic rings containing 1 to 2 oxygen atoms such asbenzodioxolyl (e.g. 1,3-benzodioxoyl, etc.); unsaturated 3 to 8 memberedrings containing an oxygen atom and 1 to 2 sulfur atoms such as, but notlimited to, dihydrooxathiinyl; saturated 3 to 8 membered ringscontaining 1 to 2 oxygen atoms and 1 to 2 sulfur atoms such as1,4-oxathiane; unsaturated condensed rings containing 1 to 2 sulfuratoms such as benzothienyl, benzodithiinyl; and unsaturated condensedheterocyclic rings containing an oxygen atom and 1 to 2 oxygen atomssuch as benzoxathiinyl. Heterocyclyl group also include those describedabove in which one or more S atoms in the ring is double-bonded to oneor two oxygen atoms (sulfoxides and sulfones). For example, heterocyclylgroups include tetrahydrothiophene, tetrahydrothiophene oxide, andtetrahydrothiophene 1,1-dioxide. Preferred heterocyclyl groups contain 5or 6 ring members. More preferred heterocyclyl groups includemorpholine, piperazine, piperidine, pyrrolidine, imidazole, pyrazole,1,2,3-triazole, 1,2,4-triazole, tetrazole, thiomorpholine,thiomorpholine in which the S atom of the thiomorpholine is bonded toone or more O atoms, pyrrole, homopiperazine, oxazolidin-2-one,pyrrolidin-2-one, oxazole, quinuclidine, thiazole, isoxazole, furan, andtetrahydrofuran.

The phrase “substituted heterocyclyl” refers to a heterocyclyl group asdefined above in which one of the ring members is bonded to anon-hydrogen atom such as described above with respect to substitutedalkyl groups and substituted aryl groups. Examples, include, but are notlimited to, 2-methylbenzimidazolyl, 5-methylbenzimidazolyl,5-chlorobenzthiazolyl, 1-methyl piperazinyl, and 2-chloropyridyl amongothers.

The phrase “aryl” refers to aryl groups that do not contain heteroatoms.Thus the phrase includes, but is not limited to, groups such as phenyl,biphenyl, anthracenyl, naphthenyl by way of example. Although the phrase“unsubstituted aryl” includes groups containing condensed rings such asnaphthalene, it does not include aryl groups that have other groups suchas alkyl or halo groups bonded to one of the ring members, as arylgroups such as tolyl are considered herein to be substituted aryl groupsas described below. A preferred unsubstituted aryl group is phenyl.Unsubstituted aryl groups may be bonded to one or more carbon atom(s),oxygen atom(s), nitrogen atom(s), and/or sulfur atom(s) in the parentcompound, however.

The phrase “substituted aryl group” has the same meaning with respect tounsubstituted aryl groups that substituted alkyl groups had with respectto unsubstituted alkyl groups. However, a substituted aryl group alsoincludes aryl groups in which one of the aromatic carbons is bonded toone of the noncarbon or non-hydrogen atoms described above and alsoincludes aryl groups in which one or more aromatic carbons of the arylgroup is bonded to a substituted and/or unsubstituted alkyl, alkenyl, oralkynyl group as defined herein. This includes bonding arrangements inwhich two carbon atoms of an aryl group are bonded to two atoms of analkyl, alkenyl, or alkynyl group to define a fused ring system (e.g.dihydronaphthyl or tetrahydronaphthyl). Thus, the phrase “substitutedaryl” includes, but is not limited to tolyl, and hydroxyphenyl amongothers. Preferred substituents include straight and branched chain alkylgroups, —CH₃, —C₂H₅, —CH₂OH, —OH, —OCH₃; —OC₂H₅, —OCF₃, —CN, —NO₂,—CO₂H, —CO₂CH₃, —CONH₂, —NH₂, —F, —Cl, Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃,—NHCOCH₃.

The term “heteroaryl”, as used herein, refers to a cyclic or bicyclicaromatic radical having from five to ten ring atoms in each ring ofwhich one atom of the cyclic or bicyclic ring is selected from S, O andN; zero, one or two ring atoms are additional heteroatoms independentlyselected from S, O and N; and the remaining ring atoms are carbon, theradical being joined to the rest of the molecule via any of the ringatoms, such as, for example, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl,pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl,oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, andnaphthyridinyl, and the like.

The term “substituted heteroaryl” as used herein refers to a heteroarylgroup as defined herein substituted by independent replacement of one,two or three of the hydrogen atoms thereon with Cl, Br, F, I, OH, CN,C₁-C₃-alkyl, C₁-C₆-alkoxy, C₁-C₆-alkoxy substituted with aryl,haloalkyl, thioalkoxy, amino, alkylamino, dialkylamino, mercapto, nitro,carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. In addition,any one substituent may be an aryl, heteroaryl, or heterocycloalkylgroup. Preferred substituents include straight and branched chain alkylgroups, —CH₃, —C₂H₅, —CH₂OH, —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂,—CO₂H, —CO₂CH₃, —CONH₂, —NH₂, —F, —Cl, Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃,—NHCOCH₃.

The term “biaryl” refers to a group or substituent to which two arylgroups, which are not condensed to each other, are bound. Exemplarybiaryl compounds include, for example, phenylbenzene, diphenyldiazene,4-methylthio-1-phenylbenzene, phenoxybenzene, (2-phenylethynyl)benzene,diphenyl ketone, (4-phenylbuta-1,3-diynyl)benzene, phenylbenzylamine,(phenylmethoxy)benzene, and the like. Preferred optionally substitutedbiaryl groups include:2-(phenylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide,1,4-diphenylbenzene,N-[4-(2-phenylethynyl)phenyl]-2-[benzylamino]acetamide,2-amino-N-[4-(2-phenylethynyl)phenyl]propanamide,2-amino-N-[4-(2-phenylethynyl)phenyl]acetamide,2-(cyclopropylamino-N-[4-(2-phenylethynyl)phenyl]acetamide,2-ethylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide,2-[(2-methylpropyl)amino]-N-[4-(2-phenylethynyl)phenyl]acetamide,5-phenyl-2H-benzo[d]1,3-dioxolene, 2-chloro-1-methoxy-4-phenylbenzene,2-[(imidazolylmethyl)amino]-N-[4-(2-phenylethynyl)phenyl]acetamide,4-phenyl-1-phenoxybenzene,N-(2-aminoethyl)[4-(2-phenylethynyl)phenyl]carboxamide,2-{[(4-fluorophenyl)methyl]amino}-N-[4-(2-phenylethynyl)phenyl]acetamide,2-{[(4-methylphenyl)methyl]amino}-N-[4-(2-phenylethynyl)phenyl]acetamide,4-phenyl-1-(trifluoromethyl)benzene, 1-butyl-4-phenylbenzene,2-cyclohexylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide,2-(ethylmethylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide,2-(butylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide,N-[4-(2-phenylethynyl)phenyl]-2-(4-pyridylamino)acetamide,N-[4-(2-phenylethynyl)phenyl]-2-quinuclidin-3-ylamino)acetamide,N-[4-(2-phenylethynyl)phenyl]pyrrolidin-2-ylcarboxamide,2-amino-3-methyl-N-[4-(2-phenylethynyl)phenyl]butanamide,4-(4-phenylbuta-1,3-diynyl)phenylamine,2-(dimethylamino)-N-[4-(4-phenylbuta-1,3-diynyl)phenyl]acetamide,2{ethylamino)-N-[4-(4-phenylbuta-1,3-diynyl)phenyl]acetamide,4-ethyl-1-phenylbenzene, 1-[4-(2-phenylethynyl)phenyl]ethan-1-one,N-(1-carbamoyl-2-hydroxypropyl)[4-(4-phenylbuta-1,3-diynyl)phenyl]carboxamide,N-[4-(2-phenylethynyl)phenyl]propanamide, 4-methoxyphenyl phenyl ketone,phenyl-N-benzamide, (tert-butoxy)-N-[(4-phenylphenyl)methyl]carboxamide,2-(3-phenylphenoxy)ethanehydroxamic acid, 3-phenylphenyl propanoate,1-(4-ethoxyphenyl)-4-methoxybenzene, and[4-(2-phenylethynyl)phenyl]pyrrole.

The term “heteroarylaryl” refers to a biaryl group where one of the arylgroups is a heteroaryl group. Exemplary heteroarylaryl groups include,for example, 2-phenylpyridine, phenylpyrrole,3-(2-phenylethynyl)pyridine, phenylpyrazole,5-(2-phenylethynyl)-1,3-dihydropyrimidine-2,4-dione, 4phenyl-1,2,3-thiadiazole, 2-(2-phenylethynyl)pyrazine,2-phenylthiophene, phenylimidazole, 3-(2-piperazinylphenyl)furan,3-2,4-dichlorophenyl)-4-methylpyrrole, and the like. Preferredoptionally substituted heteroarylaryl groups include:5-(2-phenylethynyl)pyrimidine-2-ylamine, 1-methoxy-4-(2-thienyl)benzene,1-methoxy-3-(2-thienyl)benzene, 5-methyl-2-phenylpyridine,5-methyl-3-phenylisoxazole, 2-[3-(trifluoromethyl)phenyl]furan,3-fluoro-5-(2-furyl)-2-methoxy-1-prop-2-enylbenzene,(hydroxyimino)(5-phenyl(2-thienyl))methane,5-[(4-methylpiperazinyl)methyl]-2-phenylthiophene,2-(4-ethylphenyl)thiophene, 4-methylthio-1-(2-thienyl)benzene,2-(3-nitrophenyl)thiophene,(tert-butoxy)-N-[(5-phenyl(3-pyridyl))methyl]carboxamide,hydroxy-N-[(5-phenyl(3-pyridyl))methyl]amide,2-(phenylmethylthio)pyridine, and benzylimidazole.

The term “heteroarylheteroaryl” refers to a biaryl group where both ofthe aryl groups is a heteroaryl group. Exemplary heteroarylheteroarylgroups include, for example, 3-pyridylimidazole, 2-imidazolylpyrazine,and the like. Preferred optionally substituted heteroarylheteroarylgroups include: 2-(4-piperazinyl-3-pyridyl)furan,diethyl(3-pyrazin-2-yl(4-pyridyl))amine, anddimethyl{2-[2-(5-methylpyrazin-2-yl)ethynyl](4-pyridyl)}amine.

“Optionally substituted” refers to the optional replacement of hydrogenwith one or more monovalent or divalent radicals. Optionally substitutedgroups include those described herein, for each group in which adistinct definition for substitution is supplied. Additionally, suitablesubstitution groups include, for example, hydroxyl, nitro, amino, imino,cyano, halo, thio, thioamido, amidino, imidino, oxo, oxamidino,methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, alkyl,substituted alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy,loweralkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl,heteroarylcarbonyl, heteroaralkylcarbonyl, alkylthio, aminoalkyl,cyanoalkyl, benzyl, pyridyl, pyrazolyl, pyrrole, thiophene, imidazolyl,and the like.

Representative substituted amidino and heterocycloamidino groupsinclude, for example, those shown below. These amidino andheterocycloamidino groups can be further substituted as will be apparentto those having skill in the organic and medicinal chemistry arts inconjunction with the disclosure herein.

Representative substituted alkylcarbonylamino, alkyloxycarbonylamino,aminoalkyloxycarbonylamino, and arylcarbonylamino groups include, forexample, those shown below. These groups can be further substituted aswill be apparent to those having skill in the organic and medicinalchemistry arts in conjunction with the disclosure herein.

Representative substituted aminocarbonyl groups include, for example,those shown below. These can be further substituted by heterocyclogroups and heteroaryl groups as will be apparent to those having skillin the organic and medicinal chemistry arts in conjunction with thedisclosure herein. Prefered aminocarbonyl groups include:N-(2-cyanoethyl)carboxamide, N-(3-methoxypropyl)carboxamide,N-cyclopropylcarboxamide, N-(2-hydroxy-isopropyl)carboxamide, methyl2-carbonylamino-3-hydroxypropanoate, N-(2-hydroxypropyl)carboxamide,N-(2-hydroxy-isopropyl)carboxamide,N-[2-hydroxy-1-(hydroxymethyl)ethyl]carboxamide,N-(2-carbonylaminoethyl)acetamide, N-(2-(2-pyridyl)ethyl)carboxamide,N-(2-pyridylmethyl)carboxamide, N-(oxolan-2-ylmethyl)carboxamide,N-(4-hydroxypyrrolidin-2-yl)carboxamide,N-[2-(2-hydroxyethoxy)ethyl]carboxamide,N-(4-hydroxycyclohexyl)carboxamide,N-[2-(2-oxo-4-imidazolinyl)ethyl]carboxamide,N-(carbonylaminomethyl)acetamide, N-(3-pyrrolidinylpropyl)carboxamide,N-[1-(carbonylaminomethyl)pyrrolidin-3-yl]acetamide,N-(2-morpholin-4-ylethyl)carboxamide,N-[3-(2-oxopyrrolidinyl)propyl]carboxamide,4-methyl-2-oxopiperazinecarbaldehyde,N-(2-hydroxy-3-pyrrolidinylpropyl)carboxamide,N-(2-hydroxy-3-morpholin-4-ylpropyl)carboxamide,N-{2-[(5-cyano-2-pyridyl)amino]ethyl}carboxamide,3-(dimethylamino)pyrrolidinecarbaldehyde,N-[(5-methylpyrazin-2-yl)methyl]carboxamide,2,2,2-trifluoro-N-(1-formylpyrrolidin-3-yl)acetamide,

Representative substituted alkoxycarbonyl groups include, for example,those shown below. These alkoxycarbonyl groups can be furthersubstituted as will be apparent to those having skill in the organic andmedicinal chemistry arts in conjunction with the disclosure herein.

The term “protected” with respect to hydroxyl groups, amine groups, andsulfhydryl groups refers to forms of these functionalities that areprotected from undesirable reaction with a protecting group known tothose skilled in the art such as those set forth in Protective Groups inOrganic Synthesis, Greene, T. W.; Wuts, P. G. M., John Wiley & Sons, NewYork, N.Y., (3rd Edition, 1999) that can be added or removed using theprocedures set forth therein. Examples of protected hydroxyl groupsinclude, but are not limited to, silyl ethers such as those obtained byreaction of a hydroxyl group with a reagent such as, but not limited to,t-butyldimethyl-chlorosilane, trimethylchlorosilane,triisopropylchlorosilane, triethylchlorosilane; substituted methyl andethyl ethers such as, but not limited to methoxymethyl ether,methythiomethyl ether, benzyloxymethyl ether, t-butoxymethyl ether,2-methoxyethoxymethyl ether, tetrahydropyranyl ethers, 1-ethoxyethylether, allyl ether, benzyl ether, esters such as, but not limited to,benzoylformate, formate, acetate, trichloroacetate, and trifluoracetate.Examples of protected amine groups include, but are not limited to,amides such as, formamide, acetamide, trifluoroacetamide, and benzamide;imides, such as phthalimide, and dithiosuccinimide; and others. Examplesof protected sulfhydryl groups include, but are not limited to,thioethers such as S-benzyl thioether, and S-4-picolyl thioether;substituted S-methyl derivatives such as hemithio, dithio and aminothioacetals; and others.

A “pharmaceutically acceptable salt” includes a salt with an inorganicbase, organic base, inorganic acid, organic acid, or basic or acidicamino acid. As salts of inorganic bases, the invention includes, forexample, alkali metals such as sodium or potassium; alkaline earthmetals such as calcium and magnesium or aluminum; and ammonia. As saltsof organic bases, the invention-includes, for example, trimethylamine,triethylamine, pyridine, picoline, ethanolamine, diethanolamine, andtriethanolamine. As salts of inorganic acids, the instant inventionincludes, for example, hydrochloric acid, hydroboric acid, nitric acid,sulfuric acid, and phosphoric acid. As salts of organic acids, theinstant invention includes, for example, formic acid, acetic acid,trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleicacid, citric acid, succinic acid, malic acid, methanesulfonic acid,benzenesulfonic acid, and p-toluenesulfonic acid. As salts of basicamino acids, the instant invention includes, for example, arginine,lysine and ornithine. Acidic amino acids include, for example, asparticacid and glutamic acid.

As used herein, the term “pharmaceutically acceptable ester” refers toesters that hydrolyze in vivo and include those that break down readilyin the human body to leave the parent compound or a salt thereof.Suitable ester groups include, for example, those derived frompharmaceutically acceptable aliphatic carboxylic acids, particularlyalkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which eachalkyl or alkenyl moiety advantageously has not more than 6 carbon atoms.Representative examples of particular esters include, but are notlimited to, formates, acetates, propionates, butyrates, acrylates andethylsuccinates.

The term “pharmaceutically acceptable prodrugs” as used herein refers tothose prodrugs of the compounds of the present invention that are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of humans and lower animals without undue toxicity,irritation, allergic response, and the like, commensurate with areasonable benefit/risk ratio, and effective for their intended use, aswell as the zwitterionic forms, where possible, of the compounds of theinvention. The term “prodrug” refers to compounds that are rapidlytransformed in vivo to yield the parent compound of the above formula,for example by hydrolysis in blood. A thorough discussion is provided inT. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14of the A.C.S. Symposium Series, and in Edward B. Roche, ed.,Bioreversible Carriers in Drug Design, American PharmaceuticalAssociation and Pergamon Press, 1987, both of which are incorporatedherein by reference.

The term “antibacterial agent” refers to agents synthesized or modifiedin the laboratory that have either bactericidal or bacteriostaticactivity. An “active” agent in this context will inhibit the growth ofP. aeruginosa and other gram-negative bacteria. The term “inhibiting thegrowth” indicates that the rate of increase in the numbers of apopulation of a particular bacterium is reduced. Thus, the term includessituations in which the bacterial population increases but at a reducedrate, as well as situations where the growth of the population isstopped, as well as situations where the numbers of the bacteria in thepopulation are reduced or the population even eliminated. If an enzymeactivity assay is used to screen for inhibitors, one can makemodifications in uptake/efflux, solubility, half-life, etc. to compoundsin order to correlate enzyme inhibition with growth inhibition. Theactivity of antibacterial agents is not necessarily limited to bacteriabut may also encompass activity against parasites, virus, and fungi.

The subject invention also includes isotopically-labeled LpxCinhibitors, that are structurally identical to those disclosed above,but for the fact that one or more atoms are replaced by an atom havingan atomic mass or mass number different from the atomic mass or massnumber usually found in nature. Examples of isotopes that can beincorporated into compounds of the invention include isotopes ofhydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine andchlorine, such as ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸Fand ³⁶Cl, respectively. Compounds of the present invention, prodrugsthereof, and pharmaceutically acceptable salts of said compounds and ofsaid prodrugs that contain the aforementioned isotopes and/or otherisotopes of other atoms are within the scope of this invention. Certainisotopically labeled compounds of the present invention, for examplethose into which radioactive isotopes such as ³H and ¹⁴C areincorporated, are useful in drug and/or substrate tissue distributionassays. Tritiated, i.e., ³H, and carbon-14, i.e., ¹⁴C, isotopes areparticularly preferred for their ease of preparation and detectability.Further, substitution with heavier isotopes such as deuterium, i.e., ²H,may afford certain therapeutic advantages resulting from greatermetabolic stability, for example increased in vivo half-life or reduceddosage requirements and, hence, may be preferred in some circumstances.Isotopically labeled compounds of this invention and prodrugs thereofcan generally be prepared by carrying out known or referenced proceduresand by substituting a readily available isotopically labeled reagent fora non-isotopically labeled reagent.

The present invention provides novel compounds, pharmaceuticalformulations including the compounds, methods of inhibitingUDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC),and methods of treating gram-negative bacterial infections.In one embodiment, the present invention provides compounds of formulaI:

or stereoisomers, pharmaceutically acceptable salts, esters, andprodrugs thereof, whereinE is absent or selected from the group consisting of

-   -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted C₂-C₆-alkenyl,    -   (4) substituted or unsubstituted C₂-C₆-alkynyl,    -   (5) substituted or unsubstituted aryl,    -   (6) substituted or unsubstituted heterocyclyl, and    -   (7) substituted or unsubstituted heteroaryl;        L is absent or selected from the group consisting of    -   (1) substituted or unsubstituted C₁-C₆-alkyl,    -   (2) —(NH)₀₋₁—(CH₂)_(j)—NR^(3L)—(CH₂)_(k)—,    -   (3) —(NH)₀₋₁C(R^(1L),R^(2L))—NR^(3L)—C(R^(1L),R^(2L)),    -   (4) —C(R^(1L),R^(2L))—O—C(R^(1L),R^(2L))—,    -   (5) —(CH₂)_(j)—NR^(3L)—C(R^(1L),R^(2L))—CONH—(CH₂)_(k)—,    -   (6) —CO—C(R^(1L),R^(2L))—NHCO—,    -   (7) —CONH—,    -   (8) —NHCO—,    -   wherein    -   R^(1L), R^(2L), and R^(3L) are independently selected from the        group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) C₁-C₆-alkyl substituted with aryl,        -   (d) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (e) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form, a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S,    -   j is an integer of 0-4;    -   k is an integer of 0-4;        D is absent or selected from the group consisting of    -   (1) substituted or unsubstituted C₃-C₈-cycloalkyl,    -   (2) substituted or unsubstituted aryl,    -   (3) substituted or unsubstituted heterocyclyl, and    -   (4) substituted or unsubstituted heteroaryl;        G is absent or selected from the group consisting of    -   (1) —(CH₂)_(i)—O—(CH₂)_(i)—,    -   (2) —(CH₂)_(i)—S—(CH₂)_(i)—,    -   (3) —(CH₂)_(i)—NR^(g)—(CH₂)_(i)—,    -   (4) —C(═O)—,    -   (5) —NHC(═O)—,    -   (6) —C(═O)NH—,    -   (7) —(CH₂)_(i)NHCH₂C(═O)NH—,    -   (8) —C≡C—,    -   (9) —C≡C—C≡C—, and    -   (10) —C═C—;    -   wherein    -   Rg is H or substituted or unsubstituted C₁-C₆-alkyl;    -   i is an interger of 0-4;        Y is selected from the group consisting of    -   (1) substituted or unsubstituted C₃-C₈-cycloalkyl,    -   (2) substituted or unsubstituted aryl,    -   (3) substituted or unsubstituted heterocyclyl, and    -   (4) substituted or unsubstituted heteroaryl;        X is selected from the group consisting of    -   (1) —(C═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)—,    -   (3) —C₂-C₆-alkenyl-(C═O)—,    -   (4) —C₂-C₆-alkynyl-(C═O)—, and    -   (5) —CH₂—;    -   or when B is absent, X and A, together with the atoms to which        they are attached can form a heterocyclic ring, having from 5 to        8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring        system are selected from N, O and S;        B is a absent or    -   wherein R^(1b) and R^(2b), are independently selected from the        group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) substituted or unsubstituted C₂-C₆-alkenyl,        -   (d) substituted or unsubstituted C₂-C₆-alkynyl,        -   (e) substituted or unsubstituted aryl,        -   (f) substituted or unsubstituted heterocyclyl,        -   (g) substituted or unsubstituted heteroaryl,        -   (h) C₁-C₆-alkyl substituted with aryl,        -   (i) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (j) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1b) and R^(2b) together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic: ring system are selected from N, O and S;    -   q is an integer of 0-4;        R³ is H or substituted or unsubstituted C₁-C₆-alkyl,    -   or R₃ and A, together with the atoms to which they are attached        can form a substituted or unsubstituted 3-10 membered cycloalkyl        or a heterocyclic ring system, wherein the heterocyclic ring        system may have from 3 to 10 ring atoms, with 1 to 2 rings being        in the ring system and contain from 1-4 heteroatoms selected        from N, O and S;        R₄ is H or substituted or unsubstituted C₁-C₆-alkyl,    -   or R₄ and A, together with the atoms to which they are attached        can form a substituted or unsubstituted heterocyclic ring,        having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the        heterocyclic ring system are selected from N, O and S;        n is an integer of 0-2;        A is selected from the group consisting of    -   (1) H,    -   (2) —(CH₂)_(r)C(R^(1a),R^(2a))(CH₂)_(s)OR^(3a),    -   (3) —(CH₂)_(r)C(R^(1a),R^(2a))N(R^(4a),R^(5a)),    -   (4) —(CH₂)_(r)C(R^(1a),R^(2a))N(R^(4a))COR^(3a),    -   (5) —(CH₂)_(r)C(R^(1a),R^(2a))NHCON(R^(4a),R^(5a)),    -   (6) —(CH₂)_(r)C(R^(1a),R^(2a))NHC(═NH)N(R^(4a),R^(5a)),    -   (7) —CH(R^(1a),R^(2a)),    -   (8) —C≡CH,    -   (9) —(CH₂)_(r)C(R^(1a),R^(2a))CN,    -   (10) —(CH₂)_(r)C(R^(1a),R^(2a))CO₂R^(3a), and    -   (11) —(CH₂)_(r)C(R^(1a),R^(2a))CN(R^(4a),R^(5a)),    -   wherein R^(1a), R^(2a), R^(3a), R^(4a), and R^(5a) are        independently selected from the group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) substituted or unsubstituted aryl,        -   (d) substituted or unsubstituted heterocyclyl,        -   (e) substituted or unsubstituted heteroaryl,        -   (f) C₁-C₆-alkyl substituted with aryl,        -   (g) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (h) C₁-C₆-alkyl substituted with heteroaryl,        -   or R^(4a) and R^(5a) together with the N atom to which they            are attached can form a substituted or unsubstituted            heterocyclic ring, having from 3 to 8 ring atoms, wherein            1-2 ring atoms of the heterocyclic ring system are selected            from N, O and S;    -   r is an integer of 0-4;    -   s is an integer of 0-4;        Q is absent or selected from the group consisting of    -   (1) —C(═O)N(R₁,R₂),    -   (2) —NHC(═O)N(R₁,R₂),    -   (3) —N(OH)C(═O)N(R₁,R₂),    -   (4) —CH(OH)C(═O)N(R₁,R₂),    -   (5) —CH[N(R^(2q),R^(3q))]C(═O)N(R₁,R₂),    -   (6) —CHR^(1q)C(═O)N(R₁,R₂),    -   (7) —CO₂H,    -   (8) —C(═O)NHSO₂R^(4q),    -   (9) —SO₂NH₂,    -   (10) —N(OH)C(═O)R^(1q),    -   (11) —N(OH)SO₂R^(4q),    -   (12) —NHSO₂R^(4q),    -   (13) —SH,    -   (14) —CH(SH)(CH₂)₀₋₁C(═O)N(R₁,R₂),    -   (15) —CH(SH)(CH₂)₀₋₁CO₂H,    -   (16) —H(OH)(CH₂)₀₋₁CO₂H,    -   (17) —CH(SH)CH₂CO₂R^(1q),    -   (18) —CH(OH)(CH₂)SO₂NH₂,    -   (19) —CH(CH₂SH)NHCOR^(1q),    -   (20) —H(CH₂SH)NHSO₂R^(4q),    -   (21) —H(CH₂SR^(5q))CO₂H,    -   (22) —CH(CH₂SH)NHSO₂NH₂,    -   (23) —CH(CH₂OH)CO₂H,    -   (24) —CH(CH₂OH)NHSO₂NH₂,    -   (25) —C(═O)CH₂CO₂H,    -   (26) —C(═O)(CH₂)₀₋₁CONH₂,    -   (27) —OSO₂NHR^(5q),    -   (28) —SO₂NHNH₂,    -   (29) —P(═O)(OH)₂,    -   (30)    -   (31)    -   (32)        R₁ is selected from the group consisting of    -   (1) —H,    -   (2) —OH,    -   (3) —OC₁₋₆-alkyl,    -   (4) —N(R^(2q),R^(3q)), and    -   (5) substituted or unsubstituted C₁₋₆-alkyl;        R₂ is selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted C₂-C₆-alkenyl,    -   (4) substituted or unsubstituted C₂-C₆-alkenyl,    -   (5) substituted or unsubstituted aryl,    -   (6) substituted or unsubstituted heterocyclyl,    -   (7) substituted or unsubstituted heteroaryl,    -   (8) C₁-C₆-alkyl substituted with aryl,    -   (9) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (10) C₁-C₆-alkyl substituted with heteroaryl,    -   or R¹ and R², together with the N atom to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of        the heterocyclic ring system are selected from N, O and S,    -   R^(1q), R^(2q), R^(3q), R^(4q), and R^(5q) are selected from H        or C₁-C₆ alkyl,        wherein B is absent, or E, L, G, and B are absent, or E, L, and        G are absent, or E, L, and B are absent, or E, L, D, G, and B        are absent.        In another embodiment, the present invention provides compounds        of formula I:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        E is absent or selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl, and    -   (5) substituted or unsubstituted heteroaryl;        L is absent or selected from the group consisting of    -   (1) —(CH₂)_(j)—NR^(3L)—(CH₂)_(k)—,    -   (2) —C(R^(1L),R^(2L))_(j)—NR^(3L)—C(R^(1L),R^(2L))_(k)—,    -   (3) —C(R^(1L),R^(2L))_(j)—O—C(R^(1L),R^(2L))_(k)—,    -   (4) —(CH₂)_(j)—NR^(3L)—C(R^(1L),R^(2L))_(k)—CONH—(CH₂)_(k)—,    -   (5) —CO—C(R^(1L),R^(2L))—NHCO—,    -   (6) —CONH—, and    -   (7) —NHCO—,    -   wherein    -   R^(1L), R^(2L), R^(3L) are independently selected from the group        consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) C₁-C₆-alkyl substituted with aryl,        -   (d) C₁-C₆-alkyl substituted with heterocyclyl,        -   (e) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S;    -   j is an integer of 0-4;    -   k is an integer of 0-4;        D is absent or selected from the group consisting of    -   (1) substituted or unsubstituted C₃-C₈-cycloalkyl,    -   (2) substituted or unsubstituted aryl,    -   (3) substituted or unsubstituted heterocyclyl,    -   (4) substituted or unsubstituted heteroaryl, and        G is absent or selected from the group consisting of    -   (1) —C(═O)—,    -   (2) —NHC(═O)—,    -   (3) —C(═O)NH—,    -   (4) —(CH₂)_(i)NHCH₂C(═O)NH—,    -   (5) —C≡C—, and    -   (6) —C≡C—C≡C—,    -   wherein i is an interger of 0-4;        Y is selected from the group consisting of    -   (1) substituted or unsubstituted C₃-C₈-cycloalkyl,    -   (2) substituted or unsubstituted aryl,    -   (3) substituted or unsubstituted heterocyclyl, and    -   (4) substituted or unsubstituted heteroaryl;        X is selected from the group consisting of    -   (1) —C(═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)—,    -   (3) —C₂-C₆-alkenyl-(C═O)—,    -   (4) —C₂-C₆-alkynyl-(C═O)—, and    -   (5) —CH₂—;    -   or when B is absent, X and A, together with the atoms to which        they are attached can form a heterocyclic ring, having from 5 to        8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring        system are selected from N, O and S;        B is absent or    -   wherein R^(1b) and R^(2b) are independently selected from the        group consisting of        -   (a) H        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) substituted or unsubstituted C₂-C₆-alkenyl,        -   (d) substituted or unsubstituted C₂-C₆-alkenyl,        -   (e) substituted or unsubstituted aryl,        -   (f) substituted or unsubstituted heterocyclyl,        -   (g) substituted or unsubstituted heteroaryl,        -   (h) C₁-C₆-alkyl substituted with aryl,        -   (i) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (j) C₁-C₆-alkyl substituted with heteroaryl,        -   or R^(1b) and R^(2b), together with the atoms to which they            are attached can form a substituted or unsubstituted            heterocyclic ring, having from 5 to 8 ring atoms, wherein            1-2 ring atoms of the heterocyclic ring system are selected            from N, O and S;    -   q is an integer of 0-2;        R₃ is H or substituted or unsubstituted C₁-C₆-alkyl,    -   or R₃ and A, together with the atoms to which they are attached        can form a substituted or unsubstituted 3-10 membered cycloalkyl        or a heterocyclic ring system, wherein the heterocyclic ring        system may have from 3 to 10 ring atoms, with 1 to 2 rings being        in the ring system and contain from 1-4 heteroatoms selected        from N, O and S;        R₄ is H or substituted or unsubstituted C₁-C₆-alkyl,    -   or R₄ and A, together with the atoms to which they are attached        can form a substituted or unsubstituted heterocyclic ring,        having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the        heterocyclic ring system are selected from N, O and S;        A is selected from the group consisting of    -   (1) H,    -   (2) —(CH₂)_(r)C(R^(1a),R^(2a))(CH₂)_(s)OR^(3a),    -   (3) —(CH₂)_(r)C(R^(1a),R^(2a))N(R^(4a),R^(5a)),    -   (4) —(CH₂)_(r)C(R^(1a),R^(2a))N(R^(4a))COR^(3a),    -   (5) —(CH₂)_(r)C(R^(1a),R^(2a))NHCON(R^(4a),R^(5a)),    -   (6) —(CH₂)_(r)C(R^(1a),R^(2a))NHC(═NH)N(R^(4a),R^(5a)),    -   (7) —CH(R^(1a),R^(2a)),    -   (8) —C≡CH,    -   (9) —(CH₂)_(r)C(R^(1a),R^(2a))CN, and    -   (10) —(CH₂)_(r)C(R^(1a),R^(2a))CO₂R^(3a),    -   wherein R^(1a), R^(2a), R^(3a), R^(4a), and R^(5a), are        independently selected from the group consisting of        -   (a) H,        -   (b) substituted or unsubstituted C₁-C₆-alkyl,        -   (c) C₁-C₆-alkyl substituted with aryl,        -   (d) C₁-C₆-alkyl substituted with heterocyclyl, and        -   (e) C₁-C₆-alkyl substituted with heteroaryl,        -   or R^(4a) and R^(5a), together with the N atom to which they            are attached can form a substituted or unsubstituted            heterocyclic ring, having from 5 to 8 ring atoms, wherein            1-2 ring atoms of the heterocyclic ring system are selected            from N, O and S;    -   r is an integer of 0-4;        Q is absent or selected from the group consisting of    -   (1) —C(═O)N(R₁,R₂),    -   (2) —NHC(═O)N(R₁,R₂),    -   (3) —N(OH)C(—O)N(R₁,R₂),    -   (4) —CH(OH)C(═O)N(R₁,R₂),    -   (5) —CH[N(R^(2q),R^(3q))]C(═O)N(R₁,R₂), and    -   (6) —CHR^(1q)C(═O)N(R₁,R₂),        R₁ is selected from the group consisting of    -   (1) H,    -   (2) OH,    -   (3) OC₁₋₆-alkyl,    -   (4) N(R^(2q),R^(3q)), and    -   (5) substituted or unsubstituted C₁₋₆-alkyl;        R₂ is selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl,    -   (5) substituted or unsubstituted heteroaryl,    -   (6) C₁-C₆-alkyl substituted with aryl,    -   (7) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (8) C₁-C₆-alkyl substituted with heteroaryl,    -   or R¹ and R², together with the N atom to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of        the heterocyclic ring system are selected from N, O and S,    -   R^(1q), R^(2q), and R^(3q) are selected from H or C₁-C₆alkyl,        wherein B is absent, or E, L, G, and B are absent, or E, L, and        0 are absent, or E, L, and B are absent, or E, L, D, 0, and B        are absent.        In another embodiment, the present invention provides compounds        of formula II:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;    -   X is selected from the group consisting of    -   (1) —(C═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)—, and    -   (3) —C₂-C₆-alkenyl-(C═O)—.        In another embodiment, the present invention provides compounds        of formula III:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;        X is selected from the groups consisting of    -   (1) —(C═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)—, and    -   (3) —C₂-C₆-alkenyl-(C═O)—.        In another embodiment, the present invention provides compounds        of formula IV:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;        X is selected from the groups consisting of    -   (1) —(C═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)—, and    -   (3) —C₂-C₆-alkenyl-(C═O)—.        In another embodiment, the present invention provides compounds        of formula V:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;        X is selected from the groups consisting of    -   (1) —(C═O)—,    -   (2) —C₁-C₆-alkyl-(C═O)—, and    -   (3) —C₂-C₆-alkenyl-(C═O)—.        In another embodiment, the present invention provides compounds        of formula VI:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        E is absent or selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl, and    -   (5) substituted or unsubstituted heteroaryl,    -   or E and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring-atoms of        the heterocyclic ring system are selected from N, O and S,        R^(1L), R^(3L) are independently selected from the group        consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S.        In another embodiment, the present invention provides compounds        of formula VII:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        E is absent or selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl, and    -   (5) substituted or unsubstituted heteroaryl,    -   or E and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of        the heterocyclic ring system are selected from N, O and S;        R^(1L), R^(3L) are independently selected from the group        consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S.        In another embodiment, the present invention provides compounds        of formula VIII:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        E is absent or selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl, and    -   (5) substituted or unsubstituted heteroaryl,    -   or E and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of        the heterocyclic ring system are selected from N, O and S;        R^(1L), R^(3L) are independently selected from the group        consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S.        In another embodiment, the present invention provides compounds        of formula IX:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        E is absent or selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl, and    -   (5) substituted or unsubstituted heteroaryl,    -   or E and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of        the heterocyclic ring system are selected from N, O and S;        R^(1L), R^(3L) are independently selected from the group        consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S.        In another embodiment, the present invention provides compounds        of formula X:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        E is absent or selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl, and    -   (5) substituted or unsubstituted heteroaryl,    -   or E and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted heterocyclic        ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of        the heterocyclic ring system are selected from N, O and S;        R^(1L), R^(3L) are independently selected from the group        consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl,    -   or R^(1L) and R^(3L), together with the atoms to which they are        attached can form a substituted or unsubstituted-heterocyclic        ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of        the heterocyclic ring system are selected from N, O and S.        In another embodiment, the present invention provides compounds        of formula XI:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        Y—X taken together, is selected from the group consisting of        In another embodiment, the present invention provides compounds        of formula XII:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        R^(1b) and R^(2b) are independently selected from the group        consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted C₂-C₆-alkenyl,    -   (4) substituted or unsubstituted C₂-C₆-alkenyl,    -   (5) substituted or unsubstituted aryl,    -   (6) substituted or unsubstituted heterocyclyl,    -   (7) substituted or unsubstituted heteroaryl,    -   (8) C₁-C₆-alkyl substituted with aryl,    -   (9) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (10) C₁-C₆-alkyl substituted with heteroaryl;        q is an integer of 0-2;        In another embodiment, the present invention provides compounds        of formula XIII:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        R₄ is selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl;        A is H or —CH(CH₃)OH—;        R₁ is H or substituted or unsubstituted C₁₋₆-alkyl;        R₂ is selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) substituted or unsubstituted aryl,    -   (4) substituted or unsubstituted heterocyclyl,    -   (5) substituted or unsubstituted heteroaryl,    -   (6) C₁-C₆-alkyl substituted with aryl,    -   (7) C₁-C₆-alkyl substituted with heterocyclyl,    -   (8) C₁-C₆-alkyl substituted with heteroaryl,    -   or R¹ and R² together with the N atom to which they are attached        can form a substituted or unsubstituted heterocyclic ring,        having from 3 to 10 ring atoms, wherein 1-2 ring atoms of the        heterocyclic ring system are selected from N, O and S.        In another embodiment, the present invention provides compounds        of formula XIV:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;        R₄ is selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl.        In another embodiment, the present invention provides compounds        of formula XV:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;        In another embodiment, the present invention provides compounds        of formula XVI:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;        R₄ is selected from the group consisting of    -   (1) H,    -   (2) substituted or unsubstituted C₁-C₆-alkyl,    -   (3) C₁-C₆-alkyl substituted with aryl,    -   (4) C₁-C₆-alkyl substituted with heterocyclyl, and    -   (5) C₁-C₆-alkyl substituted with heteroaryl;        In another embodiment, the present invention provides compounds        of formula XVII:        or stereoisomers, pharmaceutically acceptable salts, esters, and        prodrugs thereof, wherein        D-G-Y taken together, is selected from the group consisting of    -   Wherein    -   R is selected from the group consisting of —CH₃, —C₂H₅, —CH₂OH,        —OH, —OCH₃, —OC₂H₅, —OCF₃, —CN, —NO₂, —CO₂H, —CO₂CH₃, —CONH₂,        —NH₂, —F, —Cl, —Br, —CF₃, —N(CH₃)₂, —NHSO₂CH₃, and —NHCOCH₃;

In one aspect, the invention provides a method of inhibiting adeacetylase enzyme in a gram-negative bacteria, thereby affectingbacterial growth, comprising administering to a patient in need of suchinhibition a compound of formula I.

In another aspect, the invention provides a method of inhibiting LpxC,thereby modulating the virulence of a bacterial infection, comprisingadministering to a patient in need of such inhibition a compound offormula I.

In some embodiments of the method of inhibiting LpxC using a compound offormula I, the IC₅₀ value of the compound is less than or equal to 10 μMwith respect to LpxC. In other such embodiments, the IC₅₀ value is lessthan or equal to 1 μM, is less than or equal to 0.1 μM, is less than orequal to 0.050 μM, is less than or equal to 0.030 μM, is less than orequal to 0.025 μM, or is less than or equal to 0.010 μM.

In one aspect of the invention, methods for treating a subjectcomprising administering to the subject an antibacterially effectiveamount of a compound of formula I, together with a pharmaceuticallyacceptable carrier is provided. In a preferred embodiment of the methodof treatment, the subject is a mammal and some embodiments, a human.

In another aspect, the invention provides a method of administering aninhibitory amount of a compound of formula I to fermentative ornon-fermentative gram-negative bacteria. In a preferred embodiment ofthe method of administering an inhibitory amount of a compound offormula I to fermentative or non-fermentative gram-negative bacteria,the gram-negative bacteria are selected from the group consisting ofPseudomonas aeruginosa, Stenotrophomonas maltophila, Burkholdediacepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae,Haemophilus, Neisseria species.

In another embodiment, the invention provides a method of administeringan inhibitory amount of a compound of formula I to gram-negativebacteria, such as Enterobacteriaceae that is selected from the groupconsisting of organisms such as Serratia, Proteus, Klebsiella,Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea,and Edwardsiella species and Escherichia coli.

Another embodiment of the invention provides a pharmaceuticalcomposition comprising an effective amount of a compound of Formula Iwith a pharmaceutically acceptable carrier thereof.

Pharmaceutical formulations according to the present invention areprovided which include any of the compounds described above incombination with a pharmaceutically acceptable carrier.

Another embodiment of the invention provides a method ofco-administering the compound of formula I with other therapeutic agentsthat are selected for their particular usefulness against the conditionthat is being treated.

For example, the compound of formula I is useful in combination withother anti-bacterial agents. The compound of formula I augments thesensitivity of gram-negative bacteria to existing classes ofantibacterials. Combinations of the presently disclosed compounds withother anti-bacterial agents are within the scope of the invention. Suchanti-bacterial agents include, but are not limited to, erythromycin,rifampicin, Nalidixic acid, carbenicillin, bacitracin, cycloserine,fosfomycin, and vancomycin.

A further aspect of the invention is the use of LpxC inhibitors for thetreatment of an infection, particularly a bacterial infection. Abacterial infection treated with the compounds of the invention can be aprimary infection or a co-infection caused by a species of bacteria andone or more additional infectious agents selected from the groupconsisting of bacteria, virus, parasite and fungus.

The term “treating”, as used herein, refers to reversing, alleviating,inhibiting the progress of, or preventing the disorder or condition towhich such term applies, or one or more symptoms of such disorder orcondition. The term “treatment”, as used herein, refers to the act oftreating, as “treating” is defined immediately above.

The compounds of the invention can be used for treating conditionscaused by the bacterial production of endotoxin and, in particular, bygram-negative bacteria and bacteria that use LpxC in the biosynthesis oflipopolysaccharide (LPS) or endotoxin.

The compounds of the invention also are useful in the conditions thatare caused or exacerbated by the bacterial production of lipid A andL-PS or endotoxin, such as sepsis, septic shock, systemic inflammation,localized inflammation, chronic obstructive pulmonary disease (COPD) andacute exacerbations of chronic bronchitis (AECB). For these conditions,treatment includes the administration of a compound of the invention, ora combination of compounds of the invention, optionally with a secondagent wherein the second agent is a second antibacterial agent or asecond non-antibacterial agent.

For sepsis, septic shock, systemic inflammation, localized inflammation,chronic obstructive pulmonary disease (COPD) and acute exacerbations ofchronic bronchitis (AECB), preferred second non-antibacterial agentsinclude antiendotoxins including endotoxin receptor-binding antibodies,endotoxin-binding antibodies, antiCD14-binding protein antibodiesantilipopolysaccharide-binding protein antibodies and tyrosine kinaseinhibitors.

In treatment of serious or chronic respiratory tract infections, thecompounds of the present invention may also be used with secondnon-antibacterial agents administered via inhalation. Preferrednon-antibacterial agents used in this treatment includeanti-inflammatory steroids, non-steroidal anti-inflammatory agents,bronchiodilators, mucolytics, anti-asthma therapeutics and lung fluidsurfactants. In particular, the non-antibacterial agent may be selectedfrom a group consisting of albuterol, salbuterol, budesonide,beclomethasone, dexamethasone, nedocromil, beclometlasone, fluticasone,flunisolide, triamcinolone, ibuprofin, rofecoxib, naproxen, celecoxib,nedocromil, ipratropium, metaproterenol, pirbuterol, salmeterol,bronchiodilators, mucolytics, calfactant, beractant, poractant alfa,surfaxin and pulmozyme (also called dornase alfa).

The compounds of the invention can be used, alone or in combination witha second antibacterial agent for the treatment of a serious or chronicrespiratory tract infection including serious lung and nosocomialinfections such as those caused by Enterobacter aerogenes, Enterobactercloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca,Proteus mirabilis, Serratia marcescens, Stenotrophomonas maltophilia,Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobactercalcoaceticus, Alcaligenes xylosoxidans, Flavobacterium meningosepticum,Providencia stuartii and Citrobacter freundi, community lung infectionssuch as those caused by Haemophilus Influenzae, Legionella species,Moraxella catarrhalis, Branhamella catarrhalis, Enterobacter species,Acinetobacter species, Klebsiella species, and Proteus species, andinfections caused by other bacterial species such as Neisseria species,Shigella species, Salmonella species, Helicobacter pylori, Vibrionaceaeand Bordetella species as well as the infections is caused by a Brucellaspecies, Francisella tularensis and/or Yersinia Pestis.

When used for treating Gram-negative bacteria, the compounds of thepresent invention can be used to sensitize gram-negative bacteria to theeffects of a second agent.

When the compounds of the present invention are used in combination witha second antibacterial agent, non-limiting examples of antibacterialagents may be selected from the following groups:

-   -   (1) Macrolides or ketolides such as erythromycin, azithromycin,        clarithromycin and telithromycin;    -   (2) Beta-lactams including penicillin, cephalosporin, and        carbapenems such as carbapenem, imipenem, and meropenem;    -   (3) Monobactams such as penicillin G, penicillin V, methicillin,        oxacillin, cloxacillin, dicloxacillin, nafcillin, ampicillin,        amoxicillin, carbenicillin, ticarcillin, mezlocillin,        piperacillin, azlocillin, temocillin, cepalothin, cephapirin,        cephradine, cephaloridine, cefazolin, cefamandole, cefuroxime,        cephalexin, cefprozil, cefaclor, loracarbef, cefoxitin,        cefmetazole, cefotaxime, ceftizoxime, ceftriaxone, cefoperazone,        ceftazidime, cefixime, cefpodoxime, ceftibuten, cefdinir,        cefpirome, cefepime, and astreonam;    -   (4) Quinolones such as nalidixic acid, oxolinic acid,        norfloxacin, pefloxacin, enoxacin, ofloxacin, levofloxacin,        ciprofloxacin, temafloxacin, lomefloxacin, fleroxacin,        grepafloxacin, sparfloxacin, trovafloxacin, clinafloxacin,        gatifloxacin, moxifloxacin, sitafloxacin, ganefloxacin,        gemifloxacin and pazufloxacin;    -   (5) Antibacterial sulfonamides and antibacterial        sulphanilamides, including para-aminobenzoic acid, sulfadiazine,        sulfisoxazole, sulfamethoxazole and sulfathalidine;    -   (6) Aminoglycosides such as streptomycin, neomycin, kanamycin,        paromycin, gentamicin, tobramycin, amikacin, netilmicin,        spectinomycin, sisomicin, dibekalin and isepamicin;    -   (7) Tetracyclines such as tetracycline, chlortetracycline,        demeclocycline, minocycline, oxytetracycline, methacycline,        doxycycline;    -   (8) Rifamycins such as rifampicin (also called rifampin),        rifapentine, rifabutin, bezoxazinorifamycin and rifaximin;    -   (9) Lincosamides such as lincomycin and clindamycin;    -   (10) Glycopeptides such as vancomycin and teicoplanin;    -   (11) Streptogramins such as quinupristin and daflopristin;    -   (12) Oxazolidinones such as linezolid;    -   (13) Polymyxin, colistin and colymycin;    -   (14) Trimethoprim and bacitracin.

The second antibacterial agent may be administered in combination withthe compounds of the present inventions wherein the second antibacterialagent is administered prior to, simultaneously, or after the compound orcompounds of the present invention. When simultaneous administration ofa compound of the invention with a second agent is desired and the routeof administration is the same, then a compound of the invention may beformulated with a second agent into the same dosage form. An example ofa dosage form containing a compound of the invention and a second agentis a tablet or a capsule.

When used for treating a serious or chronic respiratory tractinfections, the compounds of the invention may be used alone or incombination with a second antibacterial agent administered viainhalation. In the case of inhalation, a preferred second antibacterialagent is selected from a group consisting of tobramycin, gentamicin,aztreonam, ciprofloxacin, polymyxin, colistin, colymycin, azithromycinand clarithromycin.

Pharmaceutical Compositions

Pharmaceutical compositions of the present invention comprise atherapeutically effective amount of a compound of the present inventionformulated together with one or more pharmaceutically acceptablecarriers. As used herein, the term “pharmaceutically acceptable carrier”means a non-toxic, inert solid, semi-solid or liquid filler, diluent,encapsulating material or formulation auxiliary of any type. Someexamples of materials that can serve as pharmaceutically acceptablecarriers are sugars such as lactose, glucose and sucrose; starches suchas corn starch and potato starch; cellulose and its derivatives such assodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate;powdered tragacanth; malt; gelatin; talc; excipients such as cocoabutter and suppository waxes; oils such as peanut oil, cottonseed oil;safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols;such a propylene glycol; esters such as ethyl oleate and ethyl laurate;agar, buffering agents such as magnesium hydroxide and aluminumhydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer'ssolution; ethyl alcohol, and phosphate buffer solutions, as well asother non-toxic compatible lubricants such as sodium lauryl sulfate andmagnesium stearate, as well as coloring agents, releasing agents,coating agents, sweetening, flavoring and perfuming agents,preservatives and antioxidants can also be present in the composition,according to the judgment of the formulator. The pharmaceuticalcompositions of this invention can be administered to humans and otheranimals orally, rectally, parenterally, intracisternally,intravaginally, intraperitoneally, topically (as by powders, ointments,or drops), bucally, or as an oral or nasal spray, or a liquid aerosol ordry powder formulation for inhalation.

Liquid dosage forms for oral administration include pharmaceuticallyacceptable emulsions, microemulsions, solutions, suspensions, syrups andelixirs. In addition to the active compounds, the liquid dosage formsmay contain inert diluents commonly used in the art such as, forexample, water or other solvents, solubilizing agents and emulsifierssuch as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethylacetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol, dimethylformamide, oils (in particular, cottonseed, groundnut,corn, germ, olive, castor, and sesame oils), glycerol,tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid estersof sorbitan, and mixtures thereof. Besides inert diluents, the oralcompositions can also include adjuvants such as wetting agents,emulsifying and suspending agents, sweetening, flavoring, and perfumingagents.

Injectable preparations, for example, sterile injectable aqueous oroleaginous suspensions may be formulated according to the known artusing suitable dispersing or wetting agents and suspending agents. Thesterile injectable preparation may also be a sterile injectablesolution, suspension or emulsion in a nontoxic parenterally acceptablediluent or solvent, for example, as a solution in 1,3-butanediol. Amongthe acceptable vehicles and solvents that may be employed are water,Ringer's solution, U.S.P. and isotonic sodium chloride solution. Inaddition, sterile, fixed oils are conventionally employed as a solventor suspending medium. For this purpose any bland fixed oil can beemployed including synthetic mono- or diglycerides. In addition, fattyacids such as oleic acid are used in the preparation of injectables.

The injectable formulations can be sterilized, for example, byfiltration through a bacterial-retaining filter, or by incorporatingsterilizing agents in the form of sterile solid compositions that can bedissolved or dispersed in sterile water or other sterile injectablemedium prior to use.

In order to prolong the effect of a drug, it is often desirable to slowthe absorption of the drug from subcutaneous or intramuscular injection.This may be accomplished by the use of a liquid suspension ofcrystalline or amorphous material with poor water solubility. The rateof absorption of the drug then depends upon its rate of dissolutionthat, in turn, may depend upon crystal size and crystalline form.Alternatively, delayed absorption of a parenterally administered drugform may be accomplished by dissolving or suspending the drug in an oilvehicle. Injectable depot forms are made by forming microencapsulematrices of the drug in biodegradable polymers such aspolylactide-polyglycolide. Depending upon the ratio of drug to polymerand the nature of the particular polymer employed, the rate of drugrelease can be controlled. Examples of other biodegradable polymersinclude poly(orthoesters) and poly(anhydrides). Depot injectableformulations may also be prepared by entrapping the drug in liposomes ormicroemulsions that are compatible with body tissues.

Compositions for rectal or vaginal administration are preferablysuppositories that can be prepared by mixing the compounds of thisinvention with suitable non-irritating excipients or carriers such ascocoa butter, polyethylene glycol or a suppository wax which are solidat ambient temperature but liquid at body temperature and therefore meltin the rectum or vaginal cavity and release the active compound.

Solid dosage forms for oral administration include capsules, tablets,pills, powders, and granules. In such solid dosage forms, the activecompound is mixed with at least one inert, pharmaceutically acceptableexcipient or carrier such as sodium citrate or dicalcium-phosphateand/or a) fillers or extenders such as starches, lactose, sucrose,glucose, mannitol, and silicic acid, b) binders such as, for example,carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone,sucrose, and acacia, c) humectants such as glycerol, d) disintegratingagents such as agar-agar, calcium carbonate, potato or tapioca starch,alginic acid, certain silicates, and sodium carbonate, e) solutionretarding agents such as paraffin, f) absorption accelerators such asquaternary ammonium compounds, g) wetting agents such as, for example,acetyl alcohol and glycerol monostearate, h) absorbents such as kaolinand bentonite clay, and i) lubricants such as talc, calcium stearate,magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate,and mixtures thereof. In the case of capsules, tablets and pills, thedosage form may also comprise buffering agents.

Solid compositions of a similar type may also be employed as fillers insoft and hard-filled gelatin capsules using such excipients as lactoseor milk sugar as well as high molecular weight polyethylene glycols andthe like.

The solid dosage forms of tablets, dragees, capsules, pills, andgranules can be prepared with coatings and shells such as entericcoatings and other coatings well known in the pharmaceutical formulatingart. They may optionally contain opacifying agents and can also be of acomposition that they release the active ingredient(s) only, orpreferentially, in a certain part of the intestinal tract, optionally,in a delayed manner. Examples of embedding compositions that can be usedinclude polymeric substances and waxes.

Solid compositions of a similar type may also be employed as fillers insoft and hard-filled gelatin capsules using such excipients as lactoseor milk sugar as well as high molecular weight polyethylene glycols andthe like.

The active compounds can also be in micro-encapsulated form with one ormore excipients as noted above. The solid dosage forms of tablets,dragees, capsules, pills, and granules can be prepared with coatings andshells such as enteric coatings, release controlling coatings and othercoatings well known in the pharmaceutical formulating art. In such soliddosage forms the active compound may be admixed with at least one inertdiluent such as sucrose, lactose or starch. Such dosage forms may alsocomprise, as is normal practice, additional substances other than inertdiluents, e.g., tableting lubricants and other tableting aids such amagnesium stearate and microcrystalline cellulose. In the case ofcapsules, tablets and pills, the dosage forms may also comprisebuffering agents. They may optionally contain opacifying agents and canalso be of a composition that they release the active ingredient(s)only, or preferentially, in a certain part of the intestinal tract,optionally, in a delayed manner. Examples of embedding compositions thatcan be used include polymeric substances and waxes.

Dosage forms for topical or transdermal administration of a compound ofthis invention include ointments, pastes, creams, lotions, gels,powders, solutions, sprays, inhalants or patches. The active componentis admixed under sterile conditions with a pharmaceutically acceptablecarrier and any needed preservatives or buffers as may be required.Ophthalmic formulations, ear drops, and the like are also contemplatedas being within the scope of this invention.

The ointments, pastes, creams and gels may contain, in addition to anactive compound of this invention, excipients such as animal andvegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulosederivatives, polyethylene glycols, silicones, bentonites, silicic acid,talc and zinc oxide, or mixtures thereof.

Compositions of the invention may also be formulated for delivery as aliquid aerosol or inhalable dry powder. Liquid aerosol formulations maybe nebulized predominantly into particle sizes that can be delivered tothe terminal and respiratory bronchioles where bacteria reside inpatients with bronchial infections, such as chronic bronchitis andpneumonia. Pathogenic bacteria are commonly present throughout airwaysdown to bronchi, bronchioli and lung parenchema, particularly interminal and respiratory bronchioles. During exacerbation of infection,bacteria can also be present in alveoli. Liquid aerosol and inhalabledry powder formulations are preferably delivered throughout theendobronchial tree to the terminal bronchioles and eventually to theparenchymal tissue.

Aerosolized formulations of the invention may be delivered using anaerosol forming device, such as a jet, vibrating porous plate orultrasonic nebulizer, preferably selected to allow the formation of aaerosol particles having with a mass medium average diameterpredominantly between 1 to 5 μm. Further, the formulation preferably hasbalanced osmolarity ionic strength and chloride concentration, and thesmallest aerosolizable volume able to deliver effective dose of thecompounds of the invention to the site of the infection. Additionally,the aerosolized formulation preferably does not impair negatively thefunctionality of the airways and does not cause undesirable sideeffects.

Aerosolization devices suitable for administration of aerosolformulations of the invention include, for example, jet, vibratingporous plate, ultrasonic nebulizers and energized dry powder inhalers,that are able to nebulize the formulation of the invention into aerosolparticle size predominantly in the size range from 1-5 μm. Predominantlyin this application means that at least 70% but preferably more than 90%of all generated aerosol particles are 1 to 5 μm range. A jet nebulizerworks by air pressure to break a liquid solution into aerosol droplets.Vibrating porous plate nebulizers work by using a sonic vacuum producedby a rapidly vibrating porous plate to extrude a solvent droplet througha porous plate. An ultrasonic nebulizer works by a piezoelectric crystalthat shears a liquid into small aerosol droplets. A variety of suitabledevices are available, including, for example, AeroNeb and AeroDosevibrating porous plate nebulizers (AeroGen, Inc., Sunnyvale, Calif.),Sidestream7 nebulizers (Medic-Aid Ltd., West Sussex, England), Pari LC7and Pari LC Star7 jet nebulizers (Pari Respiratory Equipment, Inc.,Richmond, Va.), and Aerosonic (DeVilbiss Medizinische Produkte(Deutschland) GmbH, Heiden, Germany) and UltraAire7 (Omron Healthcare,Inc., Vernon Hills, Ill.) ultrasonic nebulizers.

Compounds of the invention may also be formulated for use as topicalpowders and sprays that can contain, in addition'to the compounds ofthis invention, excipients such as lactose, talc, silicic acid, aluminumhydroxide, calcium silicates and polyamide powder, or mixtures of thesesubstances. Sprays can additionally contain customary propellants suchas chlorofluorohydrocarbons.

Transdermal patches have the added advantage of providing controlleddelivery of a compound to the body. Such dosage forms can be made bydissolving or dispensing the compound in the proper medium. Absorptionenhancers can also be used to increase the flux of the compound acrossthe skin. The rate can be controlled by either providing a ratecontrolling membrane or by dispersing the compound in a polymer matrixor gel.

According to the methods of treatment of the present invention,bacterial infections are treated or prevented in a patient such as ahuman or lower mammal by administering to the patient a therapeuticallyeffective amount of a compound of the invention, in such amounts and forsuch time as is necessary to achieve the desired result. By a“therapeutically effective amount” of a compound of the invention ismeant a sufficient amount of the compound to treat bacterial infections,at a reasonable benefit/risk ratio applicable to any medical treatment.It will be understood, however, that the total daily usage of thecompounds and compositions of the present invention will be decided bythe attending physician within the scope of sound medical judgment. Thespecific therapeutically effective dose level for any particular patientwill depend upon a variety of factors including the disorder beingtreated and the severity of the disorder, the activity of the specificcompound employed; the specific composition employed; the age, bodyweight, general health, sex and diet of the patient; the time ofadministration, route of administration, and rate of excretion of thespecific compound employed; the duration of the treatment, drugs used incombination or coincidental with the specific compound employed; andlike factors well known in the medical arts.

The total daily dose of the compounds of this invention administered toa human or other mammal in single or in divided doses can be in amounts,for example, from 0.01 to 50 mg/kg body weight or more usually from 0.1to 25 mg/kg body weight. Single dose compositions may contain suchamounts or submultiples thereof to make up the daily dose. In general,treatment regimens according to the present invention compriseadministration to a patient in need of such treatment from about 10 mgto about 2000 mg of the compound(s) of this invention per day in singleor multiple doses.

Methods of formulation are well known in the art and are disclosed, forexample, in Remington: The Science and Practice of Pharmacy, MackPublishing Company, Easton, Pa., 19th Edition (1995). Pharmaceuticalcompositions for use in the present invention can be in the form ofsterile, non-pyrogenic liquid solutions or suspensions, coated capsules,suppositories, lyophilized powders, transdermal patches or other formsknown in the art.

A “kit” as used in the instant application includes a container forcontaining the pharmaceutical compositions and may also include dividedcontainers such as a divided bottle or a divided foil packet. Thecontainer can be in any conventional shape or form as known in the artthat is made of a pharmaceutically acceptable material, for example apaper or cardboard box, a glass or plastic bottle or jar, a resealablebag (for example, to hold a “refill” of tablets for placement into adifferent container), or a blister pack with individual doses forpressing out of the pack according to a therapeutic schedule. Thecontainer employed can depend on the exact dosage form involved, forexample a conventional cardboard box would not generally be used to holda liquid suspension. It is feasible that more than one container can beused together in a single package to market a single dosage form. Forexample, tablets may be contained in a bottle that is in turn containedwithin a box.

An example of such a kit is a so-called blister pack. Blister packs arewell known in the packaging industry and are being widely used for thepackaging of pharmaceutical unit dosage forms (tablets, capsules, andthe like). Blister packs generally consist of a sheet of relativelystiff material covered with a foil of a preferably transparent plasticmaterial. During the packaging process, recesses are formed in theplastic foil. The recesses have the size and shape of individual tabletsor capsules to be packed or may have the size and shape to accommodatemultiple tablets and/or capsules to be packed. Next, the tablets orcapsules are placed in the recesses accordingly and the sheet ofrelatively stiff material is sealed against the plastic foil at the faceof the foil that is opposite from the direction in which the recesseswere formed. As a result, the tablets or capsules are individuallysealed or collectively sealed, as desired, in the recesses between theplastic foil and the sheet. Preferably the strength of the sheet is suchthat the tablets or capsules can be removed from the blister pack bymanually applying pressure on the recesses whereby an opening is formedin the sheet at the place of the recess. The tablet or capsule can thenbe removed via said opening.

It maybe desirable to provide a written memory aid, where the writtenmemory aid is of the type containing information and/or instructions forthe physician, pharmacist or other health care provider, or subject,e.g., in the form of numbers next to the tablets or capsules whereby thenumbers correspond with the days of the regimen that the tablets orcapsules so specified should be ingested or a card that contains thesame type of information. Another example of such a memory aid is acalendar printed on the card e.g., as follows “First Week, Monday,Tuesday,” . . . etc . . . “Second Week, Monday, Tuesday, . . . ” etc.Other variations of memory aids will be readily apparent. A “daily dose”can be a single tablet or capsule or several tablets or capsules to betaken on a given day. When the kit contains separate compositions, adaily dose of one or more compositions of the kit can consist of onetablet or capsule while a daily dose of another one or more compositionsof the kit can consist of several tablets or capsules.

Another specific embodiment of a kit is a dispenser designed to dispensethe daily doses one at a time in the order of their intended use.Preferably, the dispenser is equipped with a memory-aid, so as tofurther facilitate compliance with the regimen. An example of such amemory-aid is a mechanical counter, that indicates the number of dailydoses that has been dispensed. Another example of such a memory-aid is abattery-powered micro-chip memory coupled with a liquid crystal readout,or audible reminder signal that, for example, reads out the date thatthe last daily dose has been taken and/or reminds one when the next doseis to be taken.

The kits of the present invention may also include, in addition to LpxCinhibitors, one or more additional pharmaceutically active compounds.Preferably, the additional compound is another LpxC inhibitor or anothercompound useful to bacterial infections. The additional compounds may beadministered in the same dosage form as the LpxC inhibitor or indifferent dosage forms. Likewise, the additional compounds can beadministered at the same time as the LpxC inhibitor or at differenttimes.

Compositions of the present compounds may also be used in combinationwith other known antibacterial agents of similar spectrum to (1)synergistically enhance treatment of severe Gram-negative infectionscovered by the spectrum of this compound or (2) add coverage in severeinfections in which multiple organisms are suspected in which anotheragent of a different spectrum may be required in addition to thiscompound. Potential agents include members of the aminoglycosides,penicillins, cephalosporins, fluoroquinolones, macrolides,glycopeptides, lipopeptides and oxazolidinones. The treatment caninvolve administering a composition having both active agents oradministration of the inventive compounds followed by or preceded byadministration of an additional active antibacterial agent

Characterization and Purification Methods

Referring to the examples that follow, compounds of the presentinvention were characterized by high performance liquid chromatography(HPLC) using a Waters Millenium chromatography system with a 2690Separation Module (Milford, Mass.). The analytical columns were AlltimaC-18 reversed phase, 4.6×250 mm from Alltech (Deerfield, Ill.). Agradient elution was used, typically starting with 5% acetonitrile/95%water and progressing to 100% acetonitrile over a period of 40 minutes.All solvents contained 0.1% trifluoroacetic acid (TFA). Compounds weredetected by ultraviolet light (UV) absorption at either 220 or 254 nm.HPLC solvents were from Burdick and Jackson (Muskegan, Mich.), or FisherScientific (Pittsburg, Pa.). In some instances, purity was assessed bythin layer chromatography (TLC) using glass or plastic backed silica gelplates, such as, for example, Baker-Flex Silica Gel 1B2-F flexiblesheets. TLC results were readily detected visually under ultravioletlight, or by employing well known iodine vapor and other variousstaining techniques.

Mass spectrometric analysis was performed on one of two LCMSinstruments: a Waters System (Alliance HT HPLC and a Micromass ZQ massspectrometer, Column: Eclipse XDB-C18, 2.1×50 mm; solvent system: 5-95%(or 35-95%, or 65-95% or 95-95%) acetonitrile in water with 0.05% TFA;flow rate 0.8 mL/min; molecular weight range 500-1500; cone Voltage 20V; column temperature 49° C.) or a Hewlett Packard System (Series 1100HPLC; Column: Eclipse XDB-CL 8, 2.1×50 mm; solvent system: 1-95%acetonitrile in water with 0.05% TFA; flow rate 0.4 mL/min; molecularweight range 150-850; cone Voltage 50 V; column temperature 30° C.). Allmasses are reported as those of the protonated parent ions.

GCMS analysis was performed on a Hewlet Packard instrument (HP6890Series gas chromatograph with a Mass Selective Detector 5973; injectorvolume: 1 μL; initial column temperature: 50° C.; final columntemperature: 250 C; ramp time: 20 minutes; gas flow rate: 1 mL/min;column: 5% phenyl methyl siloxane, Model #HP 190915-443, dimensions:30.0 m×25 m×0.25 m).

Nuclear magnetic resonance (NMR) analysis was performed with a Varian300 Mhz NMR (Palo Alto, Calif.). The spectral reference was either TMSor the known chemical shift of the solvent. Some compound samples wererun at elevated temperatures (e.g. 75° C.) to promote increased samplesolubility.

The purity of some of the invention compounds was assessed by elementalanalysis (Desert Analytics, Tuscon, Ariz.)

Melting points were determined on a Laboratory Devices Mel-Tempapparatus (Holliston, Mass.).

Preparative separations were carried out using a Flash 40 chromatographysystem and KP-Sil, 60A (Biotage, Charlottesville, Va.), or by flashcolumn chromatography using silica gel (230-400 mesh) packing material,or by HPLC using a C-18 reversed phase column. Typical solvents employedfor the Flash 40 Biotage system and flash column chromatography weredichloromethane, methanol, ethyl acetate, hexane, acetone, aqueoushydroxyamine and triethyl amine. Typical solvents employed for thereverse phase HPLC were varying concentrations of acetonitrile and waterwith 0.1% trifluoroacetic acid.

Compounds of the present invention can be readily synthesized using themethods described herein, or other methods, that are well known in theart. For example, the synthesis of hxdroxamic acids or similar scaffoldshaving a wide variety of substituents are comprehensively reviewed inKline T, Andersen N H, Harwood E A, Bowman J, Malanda A, Endsley S,Erwin A L, Doyle M, Fong S, Harris A L, Mendelsohn B, Mdluli K, Raetz CR, Stover C K, Witte P R, Yabannavar A, Zhu S., “Potent, novel in vitroinhibitors of the Pseudomonas aeruginosa deacetylase LpxC,” J Med Chem2002 Jul. 4;45(14):3112-29; Patchett, A. A., Nargund, R., Chen, M.-H.,Nishi, H. R., U.S. Pat. No. 5,925,659, 1999; Pirrung, M. C., Chau, J.H., “A Convenient Procedure for the Preparation of Amino AcidHydroxamates from Esters,” J. Org. Chem. 1995, 60, 8084-8085; Nhu, K.,Patel, D. V., “A New and Efficient Solid Phase Synthesis of HydroxamicAcids,” J. Org. Chem. 1997, 62, 7088-7089; Patel, D., Nhu, K, “Methodsfor Solid-phase Synthesis of Hydroxylamine Compounds and Derivatives,and Combinatorial Libraries Thereof,” PCT WO 98/18754, 1998, Mellor, S.L., McGuire, C., Chan, W. C., “N-Fmoc-aminoxy-2-chlortrityl PolystyreneResin: A Facile Solid-phase Methodology for the Synthesis of HydroxamicAcids,” Tetrahedron Lett., 1997, 38, 3311-3314; Khan, S. I., Grinstaff,M. W., “A Facile and Convenient Solid-phase Procedure for SynthesizingNucleoside Hydroxamic Acids,” Terahedron. Lett., 1998, 39, 803.1-8034;Zhang, Y., Li, D., Houtman, J. C., Witiak, D. T., Seltzer, J., Bertics,P. J., Lauhon, C. T., “Design, Combinatorial Chemical Synthesis, and invitro Characterization of Novel Urea Based Gelatinase Inhibitors,”Bioorg. Med. Chem. Lett., 1999, 9, 2823-2826; Ito, Y., Inubushi, Y.,Zenbayashi, M., Tomita, S., Saegusa, T., “Synthetic Reactions by ComplexCatalysts. XXXI, A Novel and Versatile Method of Heterocycle Synthesis,”J. Am Chem. Soc., 1973, 95, 4447-4448; Ito, Y., Ito, I., Hirao, T.,Saegus, T., “Synthetic Reactions by Complex Catalysts XXXV,” Syn.Commun. 1974, 4, 97-103; Witte, H., Seliger, W., “CyclischeImidsaurester aus Nitrilen und Aminoalkoholen,” Liebigs Ann. Chem, 1974,996-1009; Pattenden, G., Thom. S. M., “Naturally Occurring Linear FusedThiazoline-Thiazole Containing Metabolites: Total Synthesis of (−)Didehydromirabazole A, a Cytotoxic Alkaloid from Blue-Green Algae,” J.Chem. Soc. Perkin Trans 1, 1993, 1629-1636; Boyce, R. J., Mulqueen, G.C., Pattenden, G., “Total Synthesis of Thiangazole, A Novel NaturallyOccurring HIV-1 Inhibitor from Polyangium sp.” Tetrahedron, 1995, 51,7321-7330; Galeotti, N., Plagnes, E., Jouin, P., “Synthesis of PeptidylAldehydes from Thiazolines,” Tetrahedron. Lett. 1997, 38, 2459-2462;Charette, A. B., Chua, P., “Mild Method for the Synthesis of Thiazolinesfrom Secondary and Tertiary Amides,” J. Org. Chem., 1998, 63, 908-909;Bergeron, R. J., Wiegand, J., McManis, J. S., McCosar, B. H., Weimar, W.R., Brittenham, G. M., Smith, R. E., “Effects of C-4 Stereochemistry andC-4′ Hydroxylation on the Iron Clearing Efficiency and Toxicity ofDesferrithiocin Analogues,” J. Med. Chem. 1999, 42, 2432-2440; Raman,P., Razavik H., Kelly, J. W., “Titanium (IV)-mediated TandemDeprotection-cyclodehydration of Protected Cysteine N-Amides: BiomimeticSynthesis of Thiazoline- and Thiazole-containing Heterocycles,” Org.Lett., 2000, 2, 3289-3292; Fernandez, X., Fellous, R., Dunach, E.,“Novel Synthesis of 2-Thioazolines,” Tetrahedron Lett., 2000, 41,3381-3384. Wipf, P., Miller, C. P., Venkatraman, S., Fritch, P., “C.Thiolysis of Oxazolinenes: A New, Selective Method for the DirectConversion of Peptide Oxazolines into Thiazolines,” Tetrahedron Lett.,1995, 36, 6395-6398, which are incorporated herein by reference.

The synthesis of other non-hydroxamates compounds or more generally zincbinding groups are reviewed in Pirrung, M. C., Turney, L. N., Raetz, C.R. H., Jackman, J. E., Snehalatha, K., McClerren, A. L., Fierke, C. A.,Gantt, S. L., Rusche, K. M., “Inhibition of the Antibacterial TargetUDP-(3-O-acyl)-N-acetylglucosamine Deacetylase (LpxC): Isoxazoline ZincAmidase Inhibitors Bearing Diverse Metal Binding Groups,” Journal ofMedicinal Chemistry (2002), 45(19), 4359-4370; Jackman, J. E., Fierke,C. A., Turney, L. N., Pirrung, M., Uchiyama, T., Tahir, S. H.,Hindsgaul, O., Raetz, C. R. H., “Antibacterial agents that target lipidA biosynthesis in gram-negative bacteria: inhibition of diverseUDP-3-O(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylases bysubstrate analogs containing zinc binding motifs,” Journal of BiologicalChemistry (2000), 275(15), 11002-11009; Brooks, C. D. W., Summers, J.B., “Modulators of Leukotriene Biosynthesis and Receptor Activation,”Journal of Medicinal Chemistry (1996), 39(14), 2629-2654; Jeng, A. Y.,De Lombaert, S., “Endothelin converting enzyme inhibitors,” CurrentPharmaceutical Design (1997), 3(6), 597-614; Zask, A., Levin, J. I.,Killar, L. M., Skotnicki, J. S., “Inhibition of matrixmetalloproteinases: structure based design,” Current PharmaceuticalDesign (1996), 2(6), 624-661; Skotnicki, J. S., DiGrandi, M. J., Levin,J. I., Chemical and Screening Sciences, Wyeth Research, New York, N.Y.,USA. Current Opinion in Drug Discovery & Development (2003), 6(5),742-759.

The foregoing may be better understood by reference to the followingexamples, that are presented for illustration and not to limit the scopeof the inventive concepts.

EXAMPLES

The following are abbreviations used in the examples:

-   -   AcOH: Acetic acid    -   aq: Aqueous    -   ATP: Adenosine triphosphate    -   Boc: tert-butoxycarbonyl    -   Boc-Thr(OBn)-OH        3-(R)-Benzyloxy-2-(S)-tert-butoxycarbonylamino-butyric acid.    -   DAP or Dap: Diaminopropionate    -   DCM:        4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran    -   DEAD: Diethyl azodicarboxylate    -   DIEA: Diisopropylethylamine    -   DME: 1,2-dimethoxyethane    -   DMF: N,N-Dimethylformamide    -   DMSO: Dimethyl sulfoxide    -   DPPA: Diphenyl phosphoryl azide    -   Et₃N: Triethylamine    -   EDC: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide    -   EDCI: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide    -   EtOAc: Ethyl acetate    -   EtOH: Ethanol    -   Fmoc: 9-fluorenylmethoxycarbonyl    -   Gly-OH: glycine    -   HATU: O-(7-azabenzotriaazol-1-yl)-N,N,N′N′=tetramethyluronium        hexafluorophophate    -   HBTU: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium        hexafluorophosphate    -   Hex: hexane    -   HOBt: butyl alcohol    -   HOBT: 1-Hydroxybenzotriazole    -   HPLC: High Pressure Liquid Chromatography    -   IC₅₀ value: The concentration of an inhibitor that causes a 50%        reduction in a measured activity.    -   iPrOH: Isopropanol    -   LC/MS: Liquid Chromatography/Mass Spectrometry    -   LRMS: Low Resolution Mass Spectrometry    -   MeOH: Methanol    -   NaOMe: sodium methoxide    -   nm: Nanometer    -   NMP: N-Methylpyrrolidone    -   PPh₃: triphenyl phosphine    -   RP-HPLC: Reversed-phase high-pressure liquid chromatography    -   RT: Room temperature    -   sat: Saturated    -   TEA: Triethylamine    -   TFA: Trifluoroacetic acid    -   THF: Tetrahydrofuran    -   Thr: Threonine    -   TLC: Thin Layer Chromatography    -   Trt-Br: Tert-butyl bromide

Nomenclature for the Example compounds was provided using ACD Nameversion 5.07 software (Nov. 14, 2001) available from Advanced ChemistryDevelopment, Inc. Some of the compounds and starting materials werenamed using standard IUPAC nomenclature.

Synthesis of N-Aroyl Threonine Analogues and Formation of Hydroxamate

Example 1 Synthesis of3-bromo-4-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide (3)

Reagent MW Eq. g/ml mmol Benzoic acid (1) 219.02 1.0 2.152 g 9.83L-Thr-OMe-HCl 169.61 1.2 1.968 g 11.6 EDCI 191.71 1.2 2.218 g 11.6 HOBt135.13 1.1 1.410 g 10.4 DIEA 129.25 4.0 6.8 mL 39.0 DMF 60 mL

Preparation of(2S,3R)-2-(3-bromo-4-fluoro-benzoylamino)-3-hydroxy-butyric acid methylester (2)

Diisopropylethylamine (6.8 mL, 39.0 mmol) was added to a stirredsolution of 3-bromo-4-fluorobenzoic acid 1 (2.152 g, 9.83 mmol),L-threonine methyl ester hydrochloride (1.968 g, 11.6 mmol), EDCI (2.218g, 11.6 mmol) and HOBt (1.410 g, 10.4 mmol) in anhydrous DMF (60 mL) at0° C. under N₂. The solution was stirred at 0° C. for 1 h and at roomtemperature for 20 h. The solution was diluted with EtOAc (300 mL) andwashed with 1.0 M HCl (2×80 mL), saturated NaHCO₃ (2×80 mL), H₂O (4×80mL), dried over MgSO₄, filtered and concentrated in vacuo to give acolorless syrup which solidified on standing to afford 3.280 g (100%) of(2S,3R)-2-(3-bromo-4-fluoro-benzoylamino)-3-hydroxy-butyric acid methylester 2 as a white solid, mp 73-74° C. MS(ES+) m/z 333.9 (C₁₂H₁₃BrFNO₄+Hrequires 334.00).

Preparation of3-bromo-4-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide(3)

To a solution of hydroxylamine hydrochloride (66 mg, 0.95 mmol) inanhydrous MeOH (2.0 mL) at 0° C. under N₂ atmosphere was added sodiummethoxide (25 wt % in MeOH, 360 mg, 1.67 mmol). A precipitate formedimmediately and the cloudy white solution was stirred for 10 minutes at0° C. A solution ofmethyl(2S,3R)-2-[(3-bromo-4-fluorophenyl)carbonylamino]-3-hydroxybutanoate(2) (284 mg, 0.850 mmol) in MeOH (2.0 mL) was added and the reactionstirred 2 h at 0° C. and then warmed gradually to room temperatureovernight (17 h total). Aqueous 1.0 M HCl (10 mL) was added and thesolution extracted with 4:1 chloroform/isopropyl alcohol (4×20 mL). Theorganic layers were combined, dried over Na₂SO₄ and concentrated to givea pink foam. The crude solid was triturated with diethyl ether (2×8 mL)and dried in vacuo to give3-bromo-4-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide3 as a white foam: mp 152-153° C. Rf (10:1 CH₂Cl₂/MeOH on silicagel)=0.53.

Preparation of Hydroxamates

Example 2 Synthesis of 4-benzoyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide

Procedure:

To a solution of hydroxylamine hydrochloride (121 mg, 1.74 mmol) inanhydrous MeOH (2.0 mL) at 0° C. under N2 atmosphere was added sodiummethoxide (25 wt % in MeOH, 680 mg, 3.14 mmol). A precipitate wasimmediately observed and the cloudy white solution was stirred for 10minutes at 0° C. A solution ofmethyl(2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoate(1) (534 mg, 1.56 mmol) in MeOH (3.0 mL) was added and the reactionstirred 3 h at 0° C., then warmed gradually to ambient temperatureovernight (18 h total). Aqueous 0.5 M HCl (20 mL) was added and thesolution extracted with 5:1 chloroform/isopropyl alcohol (4×40 mL). Theorganic layers were combined, dried over Na₂SO₄ and concentrated to givean orange foam. Purification by silica gel chromatography (increasingeluant polarity from 30:1 CH₂Cl₂/MeOH to 15:1 CH₂Cl₂/MeOH) afforded 228mg (43%) of4-benzoyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide.

Example 3 Synthesis of(2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carbohydroxamicacid Preparation of((2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-N-phenylmethoxy)carboxamide(2)

Procedure:

To a solution of(2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carboxylicacid (1) (405 mg, 1.27 mmol), benzylhydroxylamine hydrochloride (243 mg,1.52 mmol), HATU (556 mg, 1.46 mmol), and HOBt (178 mg, 1.32 mmol) inDMF (10 mL) at 0° C. was added diisopropylethylamine (710 μL, 4.07 mmol)with stirring. The cooling bath was removed after one hour and thereaction mixture stirred at ambient temperature for 18 h and thendiluted with EtOAc (200 mL). The organic layer was washed with 1.0 M HCl(2×60 mL), sat. NaHCO₃ (2×60 mL) and H₂O (5×60 mL), dried over MgSO₄ andconcentrated to give 493 mg (92%) of((2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-N-(phenylmethoxy)carboxamide(2), a colorless oil that slowly crystallized upon standing. Rf (25:1CH₂Cl₂/MeOH)=0.35.

Prepartion of(2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carbohydroxamicacid (2)

Procedure:

To a solution of((2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl-N-(phenylmethoxy)carboxamide(1) (143 mg, 0.337 mmol) in EtOH (10 mL) was added 20% Pd(OH)₂/C (50mg). The solution was purged with hydrogen gas (approx. 0.5 L from a 1 Lballoon) and then stirred under an atmosphere of H₂ (balloon pressure).TLC analysis showed no starting material after one hour. The solutionwas diluted with EtOAc (190 mL) and filtered through celite, washingwith 20:1 EtOAc/EtOH (50 mL). The solution was concentrated and dried invacuo to afford 90 mg (80%) of(2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carbohydroxamicacid (2) as a sticky white foam: mp 64-65° C. Rf (10:1CH₂Cl₂/MeOH)=0.29.

Synthesis of N-Benzyl Threonine Analogues by Reductive Amination

Example 4 Synthesis of(2S,3R)-3-hydroxy-2-([(4-phenylphenyl)methyl]amino}butanehydroxamic acid(3)

Reagent MW Eq. g/ml mmol 4-biphenylcarboxaldehyde 182.22 1.0 1.104 g6.06 L-Thr-OMe-HCl 169.61 1.0 1.030 g 6.07 NaBH(OAc)₃ 211.94 1.4 1.800 g8.49 Et₃N 101.19 2.0 1.70 mL 12.1 THF 25 mL

Triethylamine (1.70 mL, 12.1 mmol) was added to a stirred suspension ofL-threonine methyl ester hydrochloride (1.030 g, 6.07 mmol) and4-biphenylcarboxaldehyde (1.104 g, 6.06 mmol) in THF (25 mL). After 20min, NaBH(OAc)₃ was added and the suspension stirred for 20 h. Thereaction was monitored by TLC (50:1 DCM/MeOH, R_(f)=0.4). The reactionmixture was quenched with saturated NaHCO₃ (50 mL), extracted with EtOAc(2×120 mL), dried over MgSO₄, filtered and concentrated to give a yellowoil. Purification by silica gel chromatography (150:1 DCM/MeOH) afforded1.220 g (67% yield, 98% pure) of(2S,3R)-2-[(biphenyl-4-ylmethyl)-amino]-3-hydroxy-butyric acid methylester 2 as a pale yellow oil.

HPLC (260 nm, 34 min run) 14.2 min; LRMS(ES+) m/z 299.9 (C₁₈H₂₁NO₃+Hrequires 300.10). Compound 3 was then formed by the addition of NH₂OH inMeOH/NaOMe at 0° C., warming to ambient temparture of the period ofseveral hours. LCMS MH+ 301.15.General Methods for Making Phenyl-Benzoic Acids and Phenyl-BenzoateEsters (See Example 5 Below)

Suzuki Procedures Using Pd(dppf)Cl₂-DCM Catalyst and a THF/H₂O Mixture

Reagent MW EQ g/ml mmol BromoArene #1 ˜300 1 100 mg ˜0.33 Boronic Acid#2 — 1.2 — ˜0.40 Na₂CO₃ 105.99 3 104 m ˜0.99 Pd(dppf)Cl₂ 816.63 0.1-0.227-54 mg ˜0.033-0.066 THF (3) (sparged with argon for 5 min.) 0.75 mlwater(1) (sparged with argon for 5 min.) 0.25 mlStandard Procedure

1 eq aryl halide (1) was added to 1.2 eq. (2) and Pd(dppf)Cl₂ in THF,followed by addition of water and stirred 8 hours at RT. Upon completion(usually over night), the reactions are diluted with ethyl acetate (5-10ml) and water (1 ml). The organic layer is separated and washed withNaHCO₃ (2×3 ml), water (1×3 ml), brine (1×3 ml), dried with Na₂SO₄,filtered and concentrated in an 8 ml glass vial. The residue isdissolved in DMSO and injected on a preparatory HPLC reverse phasecolumn to afford >80% yield.

Suzuki Procedures Using Pd(dppf)Cl₂-DCM Catalyst and DMF Solvent

Reagent MW EQ g/ml mmol BromoArene #1 ˜500 1 20 mg ˜0.04 Boronic Acid #2˜200 2 ˜14 mg ˜0.08 Pd(dppf)Cl₂ 816.63 0.25 10 mg 0.01-0.02 TEA 101.19 528 μL ˜0.2 DMF (dry & sparged with argon for 0.5 ml 5 min.)Standard Procedure

The haloarene 1 and boronic acid 2 were weighed out and placed in thereaction flask. The DMF was sparged with argon for 5-10 minutes,followed by TEA addition, and the reaction was lightly bubbled withargon. The solid Pd(dppf)Cl₂ catalyst was added in one portion. The vialwas flushed with argon, capped tight and stirred or shaken at ˜80° C.Upon reaching completion (over night), the reaction was filtered andinjected on a preparatory HPLC reverse phase column (80% yield).

Synthesis of Methyl DAP Analogues

Example 53-(R)-Amino-2-(S)-[(4′-ethyl-biphenyl-4-carbonyl)amino]-butyl-hydroxamicacid (8)

Preparation of N-triphenylmethyl allo-threonine methyl ester (2)

Reagent MW EQ g/ml mmol H-allo-Thr-OMe-HCl (1) 169.7 1.2 2.0 g 12.0Trt-Br 323.24 1.0 3.23 g 10.0 DIEA 129.25 3.0 5.2 ml 30.0 CHCl₃ (dry)100 ml

For similar procedures see: Righi, P.; Scardovi, N.; Marotta, E.; tenHolte, P.; Zwanenburg, B. Organic Letters 2002, 4(4), 497-500.

A solution of trityl bromide (3.2 g, 10.0 mmol) in CHCl₃ (40 ml) wasadded dropwise to a stirred solution of allo-threonine methyl ester HClsalt (1) (2.0 g, 12.0 mmol) and DIEA (5.2 ml, 30.0 mmol) in CHCl₃ (60ml) at rt under N₂. The reaction could be followed by TLC eluting withEtOAc/Hex (40:60) (Rf=0.3). After stirring 12 h, the reaction wasconcentrated to a brown oil. The crude product was diluted with EtOAc(170 ml) and washed with 0.2 N citric acid (2×50 ml), water (2×50 ml),brine (50 ml), dried (Na₂SO₄), filtered and concentrated under reducedpressure to yield 3.73 g (85% yield, 95% pure) of a yellow solid.

HPLC(220 nm, 41 min. run) 30.90 min.; HPLC(220 nm, 17 min. run) 14.86min.; LCMS: LC(214 nm) 3.06 min., MS(ES+) m/z 376.2 (C₂₄H₂₅NO₃+Hrequires 376.18).

Preparation of 3-(R)-Azido-2-(S)-(trityl-amino)-butyric acid methylester (3)

Reagent MW Eq. g/ml mmol Trt-allo-Thr-OMe (2) 375.46 1.0 4.08 g 10.88PPh₃ 262.29 1.0 2.85 g 10.88 DEAD (neat) 174.16 1.6 2.93 ml 17.82 DPPA275.7 2.7 6.40 ml 29.7 THF (dry) 50 ml

For similar procedures see: Matsuda, A.; Yasuoka, J.; Sasaki, T.; Ueda,T. J. Med. Chem. 1991, 34, 999-1002.

A solution of pure DEAD (2.9 ml, 17.8 mmol) in THF (5 ml) was addedslowly dropwise to a stirred solution of trt-allo-threonine methyl ester(2) (4.1 g, 10.9 mmol) and PPh₃ (2.9 g, 10.9 mmol) in THF (40 ml) at 0°C. under N₂. After 3 min., a solution of DPPA (6.4 ml, 29.7 mmol) in THF(5 ml) was added to the orange-yellow reaction solution at 0° C. After 1h, the reaction was allowed to warm to rt. After 40 h, the reaction hadreached completion by TLC (Hexane/DCM/EtOAc (64:20:16) (Rf=0.6)) andLCMS. The yellow solution was concentrated to give 18 g of crudematerial that was purified by column chromatography eluting withHexane/EtOAc (88:12) giving 3.5 g of 70% pure product after evaporation.The product was purified again (to remove trityl alcohol and a crotylside-product formed during the reaction by elimination) by columnchromatography eluting with Hexane/DCM/EtOAc (76:20:4) giving 1.65 g(38% yield) of a pale yellow oil after concentration and drying invacuo. Note that the trityl protecting group would hydrolyze whenexposed to TFA while running the sample on HPLC.

Alternately, the reaction could be carried out in dry DCM. A reactionusing 5.44 g (14.5 mmol) of trt-allo-threonine methyl ester (2) in DCM(100 ml) with PPh₃ (3.8 g, 14.5 mmol), pure DEAD (3.4 ml, 21.8 mmol) inDCM (5 ml) and DPPA (6.3 ml, 24.0 mmol) in DCM (10 ml) were combinedfollowing the procedure above. After 3 days, the reaction did notprogress further by TLC and LCMS. After the same work up, 2.97 g of theproduct was obtained in 51% yield.

HPLC(220 nm, 41 min. run) 40.5 min.; HPLC(220 nm, 17 min. run) 16.32min.; LCMS: LC(214 nm) 3.7 min., MS(ES+) m/z 401.2 (C₂₄H₂₅N₃O₂+Hrequires 401.15).

Preparation of 2-(S)-Amino-3-(azido-butyric acid methyl ester HCl Salt(4)

Reagent MW EQ g/ml mmol Trt-Azido-Thr-OMe (3) 400.47 1.0 4.79 g 11.98TEA 57 ml CHCl₃ (dry) 3 ml

A solution of Trt-Azido-Thr-OMe (3) (4.8 g, 12.0 mmol) was dissolved ina 95% TFA/DCM solution (60 ml) at rt with stirring. After 2.5 h, thereaction was complete by LCMS. The bright yellow solution was dilutedwith 0.5 N aq. HCl (300 ml). The aqueous layer was extracted with DCM(2×30 ml) and then lyophilized to dryness. The white solid was dissolvedin AcCN/water (50:50) (100 ml) and again lyophilized to dryness toproduce a consistent powder and remove as much of the TFA as possible.The azido-Thr product (4), 2.26 g (97% yield, 95% pure) of a whitesolid, was obtained as the HCl salt.

HPLC(220 nm, 41 min. run) 7.91 min.; HPLC(220 nm, 17 min. run) 3.36 min;LCMS: LC(214 nm) 0.48 min., MS(ES+) m/z 159.3 (C₅H₁₀N₄O₂+H requires159.08).

Preparation of3-(R)-Azido-2-(S)-[(4′-ethyl-biphenyl-4-carbonyl)amino]-butyric acidmethyl ester (6)

Reagent MW EQ g/ml mmol Azido-Thr-OMe•HCl (4) 194.62 1.0 195 mg 1.0Biphenyl Acid (5) 226.27 1.0 226 mg 1.0 HOBT 153 1.0 158 mg 1.0 EDC•HCl191.17 1.3 249 mg 1.3 DIEA 129.25 2.5 0.44 ml 2.5 DCM (dry) 10 ml

A EDC.HCl (249 mg, 1.3 mmol) was added to a stirred colorless solutionof azido-Thr-OMe.HCl (4) (195 mg, 1.0 mmol), HOBT (158 mg, 1.0 mmol),4′-Ethyl-biphenyl-4-carboxylic acid (5) (226 mg, 1.0 mmol) and DIEA(0.44 ml, 2.5 mmol) in DCM (10 ml) at rt under N₂. After 24 h, thereaction had reached completion by TLC (Hexane/EtOAc (60:40) (Rf=0.3))and LCMS. The reaction was evaporated under reduced pressure to a browntar. The crude product was dissolved in EtOAc (100 ml) and washed with0.2N aq. HCl (2×50 ml), aq. sat. NaHCO₃ (50 ml), brine (50 ml), dried(Na₂SO₄), filtered and concentrated under reduced pressure to yield acrude brown solid. The crude material was further purified by columnchromatography eluting with Hexane/EtOAc (70:30) giving 245 mg (67%yield) of pure product after evaporation and drying in vacuo.

HPLC(220 nm, 41 min. run) 33.87 min.; HPLC(220 nm, 17 min. run) 15.61min; LCMS: LC(214 nm) 3.25 min., MS(ES+) m/z 367.2(C₂₀H₂N₄O₃+H requires367.17).

Preparation of3-(R)-Amino-(S)-[(4′-ethyl-biphenyl-4-carbonyl)-amino]-butyric acidmethyl ester (7)

Reagent MW EQ g/ml mmol Biphenyl Azido-Thr (6) 366.41 1.0 244 mg 0.6710% Pd/C 200 mg H₂ (gas) 12″ balloon MeOH (dry) 10 ml

A solution of biphenyl azido-Thr methyl ester (6) (244 mg, 0.67 mmol) inMeOH (10 ml) was made by sonicating until the milky precipitate cleared.After bubbling nitrogen through the reaction solution for 30 sec., 10%Pd/C was added in one portion. The reaction was stirred under nitrogenat RT. The reaction was exposed to aspirator vacuum to remove thenitrogen and then opened to the hydrogen gas at balloon pressure (˜1atm). The reaction stirred for 3 h at which time the hydrogen wasexchanged for nitrogen. The reaction was filtered through a pad ofcelite to remove the palladium. The celite pad was washed with MeOH (30ml). The combined fractions of MeOH were evaporated under reducedpressure and dried in vacuo to give 225 mg (99% yield) of pure produce(7) as a white solid.

HPLC(220 nm, 17 min. run) 10.79 min.; LCMS: LC(214 nm) 2.21 min.,MS(ES+) m/z 341.2 (C₂₀H₂₄N₂O₂+H requires 341.18).

Preparation of3-(R)-Amino-2-(S)-[(4′-ethyl-biphenyl-4-carbonyl)-amino]-butyl-hydroxamicacid (8)

Reagent MW EQ g/ml mmol Amino-Thr-OMe (7) 340.42 1.0 225 mg 0.66H₂NOH•HCl 69.49 10.0 460 mg 6.6 NaOMe 54.02 ˜12.0 ˜430 mg 7.92 MeOH(dry) 7 ml DCM (dry) 5 ml

To a stirred suspension of biphenyl-amino-Thr methyl ester (7) (225 mg,0.6 mmol) and hydroxylamine HCl salt (460 mg, 6.6 mmol) in MeOH (7 ml)and DCM (5 ml) was added fresh solid NaOMe powder (430 mg, 7.92 mmol) inone portion. After stirring for 2 min. at rt under nitrogen, the pH ofthe reaction on wet pH paper was approximately 7-8. The suspension hadchange from larger particles of white solid to a finely-divided milkyconsistency. The pH of the reaction was checked after adding smallportions of NaOMe (50-100 mg) and allowing 2 min. for the reaction toequilibrate. The pH of the reaction reached a stable 11-12 after thefinal portion of NaOMe was added (250 mg total). The reaction wasinitiated at pH 11 and proceeded quickly. After 30 min., the reactionreached 85% completion as determined by LCMS, and the reaction wasplaced in a −10° C. bath. The cold mixture filtered over fine filterpaper on a Büchner funnel. The white residue was washed with MeOH (15ml). The organic fractions were collected and concentrated under reducedpressure to give crude product (750 mg). The crude product (only one 150mg portion) was dissolved in DMSO (1 ml), AcCN (100 μl) and water (100μl), passed through a Teflon syringe filter, and the clear filtrate wasinjected on a preparative HPLC. The purification used a 20×50 mm Ultro120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA)for 16 min. The purified fractions were lyophilized to dryness. Theproduct as the TFA salt was dissolved in AcCN/water (50:50) (5 ml), 1Naq. HCl (1 equivalent) and lyophilized again to give 11.5 mg of whitepowder as an HCl salt (23% yield).

HPLC(220 nm, 41 min. run) 19.31 min.; HPLC(220 nm, 17 min. run) 9.39min; LCMS: LC(214 nm) 1.98 min., MS(ES+) m/z 342.2 (C₁₉H₂₃N₃O₃+Hrequires 342.17).

Synthesis of 4′Benzamide Biphenyl Threonine Hydroxamic Acid

Example 6 Biphenyl-4,4′-dicarboxylic acid4′-[(3-Boc-amino-propyl)amide]4-[((2R)hydroxy-(1S)-hydroxycarbamoyl-propyl)amide](6), and Example 7 Biphenyl-4,4′-dicarboxylic acid4′-[(3-amino-propyl)amide]4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide](7)

Synthesis of(2S,3R)-2-amino-3-(phenylmethoxy)-N-(phenylmethoxy)butanamide (1)

Procedure:

To a suspension of benzylhydroxylamine hydrochloride (8.310 g, 52.06mmol), Boc-Thr(OBn)-OH (14.01 g, 45.28 mmol), EDCI (10.01 g, 52.21mmol), and HOBt (6.90 g, 51.06 mmol) in CH₂Cl₂ (300 mL) at 0° C. wasadded diisopropylethylamine (28.3 mL, 162 mmol) with stiffing. Thecooling bath was removed after one hour and the reaction mixture stiffedat ambient temperature for 20 h and was then diluted with CH₂Cl₂ (300mL). The organic layer was washed with 1.0 M HCl (2×200 mL), sat. NaHCO₃(2×200 mL) and brine (200 mL), dried over MgSO₄ and concentrated to give14.5 g of a white solid. The crude solid was treated with a solution oftrifluoroacetic acid (90 mL) in CH₂Cl₂ (90 mL) and stirred for 2.5 h.The reaction mixture was concentrated by rotary evaporation and thendiluted with CH₂Cl₂ (600 mL). The organic layer was washed with sat.NaHCO₃ (2×200 mL), dried over MgSO₄ and concentrated to give a darkorange oil. Purification by silica gel chromatography (50:1 CH₂Cl₂/MeOH)afforded (2S,3R)-2-amino-3-(phenylmethoxy)-N-(phenylmethoxy)butanamide(A) (8.9 g,) as a pale yellow oil. Rf (50:1 CH₂Cl₂/MeOH on silicagel)=0.2.

Preparation of(1S,2R)-4′-(2-benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)biphenyl-4-carboxylicacid (3)

Reagent MW Eq. g/mL mmol Amine (1) 314.38 1.0 0.944 g 3.00 Dicarboxylicacid (2) 242.23 1.9 1.360 g 5.61 BOP 442.3 1.5 2.007 g 4.54 DIEA 129.253.3 1.7 mL 9.76 DMF 200 mL

To a suspension of 4,4′-biphenyldicarboxylic acid 2 (1.360 g, 5.61 mmol)in DMF (180 mL) was added BOP (2.007 g, 4.54 mmol) and DIEA (1.7 mL, 9.8mmol). A solution of (1S,2R)-2-amino-3,N-bis-benzyloxy-butyramide 1 (944mg, 3.00 mmol) in DMF (20 mL) was added and the reaction stirred for 18h. The solution was diluted with EtOAc (250 mL) and washed with 1.0 MHCl (500 mL). The aqueous layer was extracted with EtOAc (250 mL) andthe organic layers combined. The organic layer was washed with 1.0 M HCl(250 mL), dried over MgSO₄, and concentrated to give a crude yellowsolid. Purification by silica gel chromatography (60:1 CH₂Cl₂/MeOH) gave210 mg(1S,2R)-4′-(2-benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylicacid 3. (13% yield) as a yellow solid. R_(f)=0.80 (10:1 CH₂Cl₂/MeOH);LRMS (ES+) m/z 539.1 (C₃₂H₃₀N₂O₆+H requires 539.22).

Preparation of biphenyl-4,4′-dicarboxylic acid4′-[(3-Boc)-amino-propyl)-amide]-4-[(2R)-benzyloxy(1S)-benzyloxycarbamoyl-propyl)-amide](5)

Reagent MW Eq. g/mL mmol Biphenylcarboxylic acid (3) 538.59 1.0 0.200 g0.371 Amine (4) 174.24 1.1 0.071 g 0.407 EDCI 191.71 1.1 0.078 g 0.407HOBt 135.13 1.0 0.052 g 0.385 DIEA 129.25 2.7 180 μL 1.0 DMF 2 mL

To a solution of biphenylcarboxylic acid 3 (200 mg, 0.371 mmol), EDCI(78 mg, 0.407 mmol), and HOBt (52 mg, 0.385 mmol) in DMF (2 mL) wasadded t-Butyl N-(3-aminopropyl)carbamate 4 (71 mg, 0.407 mmol) and DIEA(180 μL, 1.0 mmol). The reaction mixture was stirred 24 h, diluted withEtOAc (150 mL), washed with 1.0 M HCl (2×60 mL), saturated NaHCO₃ (2×60mL), H₂O (3×60 mL), dried over MgSO₄ and concentrated to give a crudewhite solid. Purification by silica gel chromatography (25:1CH₂Cl₂/MeOH) afforded 194 mg (75% yield) of biphenyl-4,4′-dicarboxylicacid4′-[(3-(Boc)amino-propyl)-amide]4-[(2R)-benzyloxy-(1S)-benzyloxycarbamoyl-propyl)-amide]5 as a white solid. R_(f)=0.15 (50:1 CH₂Cl₂/MeOH); LRMS (ES+) m/z 695.2(C₄₀H₄₆N₄O₇+H requires 695.35).

Preparation of Biphenyl-4,4′-dicarboxylic acid4′-[(3-Boc-amino-propyl)amide]4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)amide](6)

Reagent MW Eq. g/mL mmol Biphenyl diamide (5) 694.82 1.00 0.190 g 0.273Pd(OH)₂ (20%/C) 106.42 0.15 0.020 g 0.040 H₂ (g) balloon THF  5.0 mLMeOH  3.0 mL

A solution of dibenzyl-protected threonine hydroxamic acid 5 (190 mg,0.273 mmol) in THF (5 mL) and MeOH (3 mL) was charged with Pd(OH)₂(20%/C, 20 mg, 0.04 mmol) and stirred under a hydrogen atmosphere(balloon pressure) for 16 h. The crude mixture was filtered through aplug of celite eluting with 2:1 MeOH/THF (15 mL) and concentrated togive an orange syrup. Purification by silica gel chromatography (5:1:1THF/MeOH/CH₂Cl₂ afforded 110 mg (78% yield) ofbiphenyl-4,4′-dicarboxylic acid4′-[(3-Boc-amino-propyl)-amide]4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide]as a white foam, mp 75-77° C. R_(f)=0.20 (10:1 CH₂Cl₂/MeOH); LRMS (ES+)m/z 515.4 (C₂₆H₃₄N₄O₇+H requires 515.26).

Preparation of Biphenyl-4,4′-dicarboxylic acid4′-[(3-amino-propyl)-amide]4-[((2R)hydroxy-(1S)-hydroxycarbamoyl-propyl)amide](7)

Reagent MW Eq. g/mL mmol Boc-protected amine (6) 514.57 1.00 0.080 g0.155 TFA 3.0 mL CH₂Cl₂ 3.0 mL

A flask containing Boc-protected amine 6 (80 mg, 0.155 mmol) was treatedwith 50% TFA/CH₂Cl₂ (6.0 mL) and stirred for 2.5 h. The reaction mixturewas concentrated by rotary evaporation to give a brown syrup.Purification by RP-HPLC (C₁₈ column, CH₃CN gradient 5-70%, 0.1% TFA, UVanalysis 300 nm, 36 min) and lyophilization of the collected fractionsafforded 14 mg (21% yield) of biphenyl-4,4′-dicarboxylic acid4′-[(3-amino-propyl)-amide]4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide]as a white solid. LRMS (ES+) m/z 415.3 (C₂₁H₂₆N₄O₅+H requires 415.20);RP-HPLC (300 nm, 36 min run) 18.2 min.

Example 8 Synthesis ofN-(2-(N-hydroxycarbamoyl)(2S)-2-{[4-(4-ethylphenyl)phenyl]carbonylamino}ethyl)acetamide(4)

Preparation of3-Acetylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (2)

Reagent MW EQ g/ml mmol Fmoc-DALP-H (1) 326.4 1.0 980 mg 3.0 Aceticanhydride 102.09 1.5 425 uL 4.5 Pyridine 79.1 2.0 483 uL 6.0 THF  20 ml

Acetic anhydride in THF (5 ml) was added to a cloudy mixture ofFmoc-DAP-H (1) (980 mg, 3.0 mmol) and pyridine (483 uL, 6.0 mmol) in THF(15 ml) with stirring at rt. After 4 hours, the clear pale yellowsolution had reacted completely by LCMS. The reaction was evaporatedunder reduced pressure. The residue was dissolved in EtOAc (150 ml) andwashed with 0.1M NaHSO₄ (50 ml), water (50 ml), sat. brine (50 ml),dried with Na₂SO₄, filtered and concentrated under reduced pressure togive 1.1 g of crude product as a white solid. The crude product waspurified by prep. HPLC to give 0.99 g (90% yield) of acyl-DAP (2).

Preparation of (2-Acetylamino-1-hydroxycarbamoyl-ethyl)-carbamic acid9H-fluoren-9-ylmethyl ester trityl resin (3)

Reagent MW EQ g/ml mmol H₂N—O-Th Resin 1.0 120 mg 0.113 Fmoc-DAP(Ac)-H(1) 368.4 5.0 980 mg 0.564 HATU 380 5.0 0.146 g 0.564 DIBA 129.25 10.0196 ul 1.13 NMP 1.7 ml

A solution of Fmoc-DAP(Ac)-H (1) (980 mg, 0.56 mmol), HATU (0.146 g,0.56 mmol) in NMP (1.7 ml) was made. After 2 min. of shaking, theactivated acid was added to the deprotected H₂N-O-Trt Resin (120 mg,0.113 mmol) at rt with shaking. [Deprotection of the Fmoc group from theresin was accomplished using 20% piperizine in DMF (4 ml) for 2 hourstwice. The resin was drained and washed with DMF (2×5 ml) and DCM (2×5ml).] After shaking for 20 hours, the reaction was drained and washedwith DMF (2×5 ml) and DCM (2×5 ml). The resin was dried and used as isin the next reaction.

Preparation ofN-(2-(N-hydroxycarbamoyl)(2S)-2-{[4-(4-ethylphenyl)phenyl]carbonylamino}ethyl)acetamide(4) Preparation of (2-Acetylamino-1-hydroxycarbamoyl-ethyl)carbamic acid9H-fluoren-9-ylmethyl ester trityl resin (3)

Reagent MW EQ g/ml mmol Fmoc-DAP(Ac)-Trt Resin (3) 1.0 120 mg 0.1134′-Etbiphenyl 4-carboxy acid 226.3 5.0 91 mg 0.4 HATU 380 5.0 152 mg 0.4DIEA 129.25 10.0 140 ul 0.8 NMP 1.0 ml

The resin was treated with 20% piperizine in DMF (4 ml) for 2 hourstwice. The resin was drained and washed with DMF (2×5 ml) and DCM (2×5ml). The resin was dried in vacuo. A solution of4′-Ethyl-biphenyl-4-carboxylic acid (91 mg, 0.4 mmol), HATU (152 g, 0.4mmol) in NMP (1.0 ml) was made. After 2 min. of shaking, the activatedacid was added to the deprotected H-DAP(Ac)-Trt resin (120 mg, 0.113mmol) at rt with shaking. After shaking for 18 hours, the reaction wasdrained and washed with DMF (2×5 ml) and DCM (2×5 ml). The resin wasdried in vacuo. The product was cleaved from the resin through treatmentwith a solution of TFA (500 uL), DCM (500 uL) and water (50 uL) for 25min. The resin was filtered and washed with fresh DCM (2 ml). Thecombined TFA and DCM fractions are evaporated under reduced pressure.The residue was diluted with CH₃CN/water (1:1) (10 ml) and lyophilized.The crude product was purified by prep. HPLC. The crude product wasdissolved in DMSO (1 ml), passed through a Teflon syringe filter, andthe clear filtrate was injected on a preparative HPLC. The purificationused a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient(AcCN/water, 0.1% TFA) for 16 min. The purified fractions werelyophilized to dryness. The solid residue was lyophilized again fromCH₃CN/water (1:1) (5 ml) give 8.6 mg of pure product (4) (˜21% yield).

Example 9 Synthesis of 4′-Ethyl-biphenyl-4-carboxylic acid(1-hydroxycarbamoyl-2-methanesulfonylamino-ethyl)amide (3) Preparationof 4′-Ethyl-biphenyl-4-carboxylic acid(2-amino-1-hydroxycarbamoyl-ethyl)-amide trityl resin (2)

Reagent MW EQ g/ml mmol Biphenyl-DAP(Alloc)-Trt Resin (1) 1.0  500 mg0.35 Dimethyl barbituric acid 156.14 10.0  600 mg 3.5 Pd(PPh₃)₄ 1135.61.0  438 mg 0.35 PPh₃ 262.3 2.0  202 mg 0.7 DCM 11.0 ml

Pd(PPh₃)₄ (438 mg, 0.35 mmol) was added to a vial containingbiphenyl-DAP(Alloc)-Trt Resin (1) (500 mg, 0.35 mmol), Dimethylbarbituric acid (600 mg, 3.5 mmol) and PPh₃ (438 mg, 0.35 mmol) in DCM(11 ml) at rt under argon. The mixture was sparged with argon and shakenfor 16 hours. The bright yellow mixture was drained and washed with DMF(8×10 ml) and DCM (8×10 ml). The resin was dried in vacuo to give thedeprotected DAP resin 2.

Preparation of 4′-Ethyl-biphenyl-4-carboxylic acid(1-hydroxycarbamoyl-2-methane sulfonylamino-ethyl)amide (3)

Reagent MW EQ g/ml mmol Biphenyl-DALP-Trt Resin (2) 1.0 160 mg 0.11Methanesulfonyl chloride 114.55 10.0  85 uL 1.1 Lutidine 107.16 15.0 190uL 1.6 DCM  1.5 ml

Methanesulfonyl chloride (85 uL, 1.1 mmol) was added to a mixture ofdeprotected DAP resin (2) (160 mg, 0.11 mmol) and lutidine (190 uL, 1.6mmol) in DCM (1.5 ml). After shaking for 16 hours, the mixture wasdrained and washed with DMF (10×2 ml) and DCM (5×2 ml). The product wascleaved from the resin through treatment with TFA/water (4:1) (1.5 ml).After shaking for 45 min., the TFA solution was collected from the resinby filtration, and the resin was washed with TFA (1 ml) and TFA/water(1:1) (10 ml). The combined TFA fractions were concentrated underreduced pressure to a reddish-brown solid. The product, identified byLCMS, was purified by prep. HPLC using a 20×50 mm Ultro 120 C18 columnrunning a 22 ml/min 4% gradient (AcCN/water, 0.1% TFA) for 16 min. Thepurified fractions were lyophilized to dryness. The solid residue waslyophilized again from CH₃CN/water (1:1) (5 ml) give 4 mg of pureproduct as a white solid (3) (˜9% yield).

Example 10 Synthesis of 4′-Ethyl-biphenyl-4-carboxylic acid[2-(3,3-dimethyl-ureido-1-hydroxycarbamoyl-ethyl]-amide (3) (Continuedfrom Compound 2 of Example 9 Above)

Reagent MW EQ g/ml mmol Biphenyl-DAP-Trt Resin (2) 1.0 125 mg 0.096Dimethylcarbamyl chloride 107.5 10.0 103 mg 0.96 Lutidine 107.16 20.0225 uL 1.92 DCM  1.5 ml

Dimethylcarbamyl chloride (103 mg, 0.96 mmol) was added to a mixture ofdeprotected DAP resin (2) (125 mg, 0.096 mmol) and lutidine (225 uL,1.92 mmol) in DCM (1.5 ml). After shaking at rt for 5 hours, the mixturewas drained and washed with DCM (5×2 ml), DMF (5×2 ml) and DCM (5×2 ml).The product was cleaved from the resin through treatment with TFA/water(4:1) (1.5 ml). After shaking for 45 min., the TFA solution wascollected from the resin by filtration, and the resin was washed withTFA/water (1:1) (2 ml). The combined TFA fractions were concentratedunder reduced pressure to a reddish-brown solid. The product, identifiedby LCMS, was purified by prep. HPLC using a 20×50 nun Ultro 120 C18column running a 22 ml/min 4% gradient (AcCN/water, 0.1% TFA) for 16min. The purified fractions were lyophilized to dryness. The solidresidue was lyophilized again from CH₃CN/water (1:1) (5 ml) give 5 mg ofpure product as a white solid (3) (˜13% yield).

Example 11 Synthesis of 4′-Ethyl-biphenyl-4-carboxylic acid[2-(2-amino-ethylamino)-1-hydroxycarbamoyl-ethyl]-amide (2)

Reagent MW EQ g/ml mmol Biphenyl-DAP-hydroxamate (1) 327.4 1.0  20 mg0.096 Boc-amino-acetaldehyde 159.19 4.0 6.4 mg 0.4 NaBH₃CN 62.84 10.03.1 mg 0.05 Acetic acid 60.05 20.0   6 uL 1.00 DCM 1.5 ml

NaBH₃CN (3.1 mg, 0.05 mmol) followed by acetic acid (6 uL, 1.0 mmol)were sequentially added to a stirred suspension ofbiphenyl-DAP-hydroxamate (1) (20 mg, 0.096 mmol) andBoc-amino-acetaldehyde (6.4 mg, 0.4 mmol) in MeOH (1.5 ml) in a 4 mlvial. The reaction was followed by LCMS. After stirring 12 hours, thecloudy reaction was only 50% complete. The reaction was concentratedunder reduced pressure to a thick slurry that was dissolved in DMSO. Theproduct was purified by prep. HPLC using a 20×50 mm Ultro 120 C18 columnrunning a 22 ml/min 3% gradient (AcCN/water, 0.1% TFA) for 16 min. Thepurified fractions were lyophilized to dryness. The dried powder wasdissolved in CH₃CN/water (1:1) (1 ml) and 1M HCl (700 uL). After heatingat 50° C. for 75 min., the reaction mixture was again lyophilized todryness to produce 7.1 mg of product (2) as a 2×HCl salt white powder(˜17% yield).

Example 12 Synthesis ofN-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxypropyl)[4-(2-phenylethynyl)phenyl]carboxamide

Preparation of 4-Phenylethynyl-benzoic acid (3)

Reagent MW EQ g/ml mmol Iodo-benzoate 1 262 1.0 20.0 g 76.34Ethynyl-benzene 2 102 1.1 8.56 g 83.96 PdCl₂(PPh₃)₂ 702 0.012 0.65 g0.92 Cul 190 0.024 0.35 g 1.83 TEA 101 1.5   16 ml 114.5 d= 0.726 THF(dry & sparged 110 ml with argon for 5 min.)

The 4-iodo-benzoic acid methyl ester 1 (20.0 g, 76.34 mmol),ethynyl-benzene 2 (8.56 g, 83.96 mmol), PdCl₂(PPh₃)₂ (0.65 g, 0.92mmol), and CuI (0.35 g, 1.83 mmol) were mixed with THF (110 ml) in around bottom under argon. The dry THF was sparged with dry, oxygen-freeargon for at least 5 min. immediately before use. The reaction wascooled to 10° C. and TEA (16 ml) was added. The cooling bath was removedand the reaction was stirred at RT under argon. After 2.5 h, thereaction was diluted with EtOAc (400 ml) and the solids were filteredoff through a pad of celite. The organic filtrate was washed with 1M HCl(60 ml), sat. aq. NaHCO₃ (60 ml), water (60 ml), brine (60 ml), driedwith Na₂SO₄, filtered and concentrated under reduced pressure. The crudesolid methyl ester was dissolved in MeOH (400 ml), 6M NaOH (30 ml) andwater (50 ml). The reaction was stirred at 70° C. until a clear solutionwas formed (about 1 h). The reaction could be followed by LCMS. Thereaction was cooled and diluted with water (500 ml) and hexane (100 ml).The pH was adjusted to pH 6-7. The white solid that formed was collectedand washed with water (3×60 ml) and hexane (3×60 ml). The solid 3 wasdried in vacuo yielding 17.3 g (approximately quantitative yield in 99%purity).

Preperation of 3′-Hydroxy-2-(4-phenylethynyl-benzoylamino)butyric acidmethyl ester (4)

Reagent MW EQ g/ml mmol 4-Phenylethynyl-benzoic acid (3) 222 1.0 1.55 g7.0 Threonine methyl ester · HCl 169.65 1.4 1.66 g 9.8 HBTU 380 1.0 2.66g 7.0 DIEA 125.28 2.5 3.05 ml 17.5 DMF   21 ml

A solution of threonine (1.66 g, 9.8 mmol) and DIEA (1.53 ml, 8.8 mmol)in DMF (10 ml) was added to a stirred solution of4-phenylethynyl-benzoic acid 3 (1.55 g, 7.0 mmol) and DIEA (1.53 ml, 8.8mmol) in DMF (11 ml) at rt. After 12 h, the reaction was diluted withEtOAc (300 ml) and washed with 0.5M HCl (2×60 ml), sat aq. NaHCO₃ (60ml), 50% diluted brine (60 ml), sat. brine (60 ml), dried with Na₂SO₄,filtered and concentrated under reduced pressure. Upon drying in vacuo,2.34 g of white solid was obtained (approximately quantitative yield in99% purity).

Preperation ofN-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide (5)

Reagent MW EQ g/ml mmol Tolanoic-Thr-OMe (4) 340.42 1.0 2.34 g 7.0H₂NOH.HCl 69.49 10.0 4.81 g 70.0 NaOMe 54.02 >11.0 >4.16 g >77.0 MeOH(dry) 50 ml DCM (dry) 30 ml

A solution of tolanoic-Thr methyl ester (4) (2.34 g, 7.0 mmol) in MeOH(20 ml) and DCM (30 ml) was added to a cooled (−10° C. bath) suspensionof hydroxylamine HCl salt (4.81 g, 70.0 mmol) and NaOMe (4.16 g, 77.0mmol) in MeOH (30 ml). Follow reaction by LCMS. After stirring for 2hours, the reaction seems to stall at 50% completion. Add an additional1 equivalent of NaOMe (0.416 g). After 3 hours, the reaction was 75%complete. Add an additional 0.5 equivalent of NaOMe (0.21 g). After 4hours, the reaction was 90% complete. Add an additional 0.15 equivalentof NaOMe (0.064 g) for a total of 12.65 equivalents of NaOMe. The pH ofthe reaction was between 11-12 and had reacted about 95% completion. Thereaction was diluted with EtOAc (500 ml) and washed with sat. aq. NaHCO₃(2×60 ml), 50% diluted brine (60 ml), sat brine (60 ml), dried withNa₂SO₄, filtered and concentrated under reduced pressure. The residuewas dissolved in minimal DMA. The product was purified by prep. HPLCusing a reverse phase Ultro 120 C18 column running a 2% gradient(AcCN/water, 0.1% TFA). The purified fractions were lyophilized todryness. The product as the TFA salt was dissolved in AcCN/water (50:50)(80 ml), 1N aq. HCl (13 equivalent) and lyophilized again to give 1.3 gof white powder in 55% yield and >97% purity.

Example 13 Synthesis of3-(R)-Amino-2-(S)-3-phenylethynyl-benzoylamino)butyl-hydroxamic acid(10) Preparation of3-(R)-Azido-2-S-(3-phenylethynyl-benzoylamino)-butyric acid methyl ester(9)

The synthesis of compound 4 is described above. The tolanyl compound (9)was made by the same procedures as for compound (6). The product (9) wasobtained in 92% yield (952 mg).

HPLC(220 nm, 41 min. run) 32.64 min.; HPLC(220 nm, 17 min. run) 15.08min LCMS: LC(214 nm) 3.16 min., MS(ES+) m/z 363.1 (C₂₀H₁₈N₄O₃+H requires363.14).

Preparation of3-(R)-Amino-2-(S)-(3-phenylethynyl-benzoylamino)-butyl-hydroxamic acid(10)

Reagent MW Eq. g/ml mmol Amino-Thr-OMe (9) 362.38 1.0 726 mg 2.0 PPh₃262.29 1.0 526 mg 2.0 H₂NOH.HCl 69.49 10.0  1.4 g 20.0 NaOMe 54.02 ˜12.0 1.3 g 24.0 THF(dry)  20 ml MeOH (dry)  20 ml

Triphenylphosphine (526 mg, 2.0 mmol) was added to a stirred solution oftolanyl-azido-Thr methyl ester (9) (726 mg, 2.0 mmol) at rt. After 3days the reaction reached completion as judged by TLC (EtOAc/Hex (2:1))and LCMS. The reaction was concentrated under reduced pressure to givean ivory colored solid. The crude amino-phosphine was dissolved in MeOH(20 ml) to give a pale yellow solution. To the solution ofamino-phosphine was added sequentially hydroxylamine HCl salt (1.4 g,20.0 mmol) followed by fresh solid NaOMe powder (1.3 g, 24.0 mmol) tomake a milky pH 10 suspension. After 36 h, the reaction was complete byLCMS. The reaction was evaporated under reduced pressure to give ayellow solid that was dried in vacuo. The crude product (2.75 g) wastriturated with ether (3×50 ml) to remove impurities (P(O)Ph₃) and thenwas dissolved in abs. EtOH (120 ml) with sonication for 15 min. A finewhite powder was suction filtered off, and the clear yellow ethanolicportion was concentrated to a small volume. The crude product wasdissolved in DMSO (8 ml) and purified by preparative HPLC (Ultro 120 C1875×300 mm column) running a gradient (AcCN/water, 0.1% TFA) from 5 to70% for 55 min. The purified fractions were pooled together andlyophilized to dryness. The product as the TFA salt was dissolved inAcCN/water (50:50) (100 ml), 1N aq. HCl (1 equivalent) and lyophilizedagain to give 325 mg of light yellow powder as the HCl salt (43% yield).

HPLC(220 nm, 41 min. run) 18.31 min.; HPLC(220 nm, 17 min. run) 9.11min; LCMS: LC(214 nm) 1.91 min., MS(ES+) m/z 338.1 (C₁₉H₁₉N₃O₃+Hrequires 338.14).

Synthesis of 4′-(N-Acylamino)-Tolan Dap Analogs

Example 14 Synthesis of4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide

Preparation of 2-N-Boc-amino-N-iodo-phenylacetamide (2)

Reagent MW Eq. g/ml mmol Boc-Gly-OH 175.19 1.00 1.752 g 10.04-Iodoaniline (1) 219.03 1.04 2.290 g 10.4 EDCI 191.71 1.04 1.994 g 10.4HOBt 135.13 1.00 1.351 g 10.0 DCM   18 mL DMF    1 mL

A solution of Boc-Gly-OH (1.752 g, 10.0 mmol) in DCM (18 mL) and DMF (1mL) was treated with EDCI (1.994 g, 10.4 mmol) and HOBt (1.351 g, 10.0mmol). After stirring 15 min, 4-iodoaniline 1 (2.290 g, 10.4 mmol) wasadded and the reaction monitored by TLC (25:1 DCM/MeOH (R_(f)=0.6)).After 24 h the solution was diluted with EtOAc (250 mL), washed with 1.0M HCl (3×100 mL), sat. NaHCO₃ (3×100 mL), brine (3×100 mL), dried overMgSO₄, filtered and concentrated in vacuo to afford 2.900 g (77% yield)of a white solid.

Preparation of (2S)-3-N-Boc-amino(4-ethynyl-benzoylamino)propionic acidmethyl ester (4)

Reagent MW Eq. g/mL mmol 4-Ethynylbenzoic acid (3) 146.14 1.0 0.910 g6.22 H-Dap(Boc)-OMe-HCl 254.71 1.2 1.903 g 7.47 EDCI 191.71 1.2 1.432 g7.47 HOBt 135.13 1.1 0.910 g 6.73 DIEA 129.25 3.2  3.5 mL 20.0 DMF   50mL

Triethylamine (3.5 mL, 20.0 mmol) was added to a stirred solution of4-ethynylbenzoic acid 3 (910 mg, 6.22 mmol), H-Dap(Boc)-OMehydrochloride (1.903 g, 7.47 mmol), EDCI (1.432 g, 7.47 mmol), and HOBt(910 mg, 6.73 mmol) in DMF (50.0 mL). After stirring 20 h, the reactionmixture was diluted with EtOAc (400 mL), washed with 1.0 M HCl (2×100mL), saturated NaHCO₃ (2×100 mL), H₂O (4×100 mL), dried over MgSO₄,filtered and concentrated in vacuo to give 2.140 g (99% yield) of a tansolid, mp=110-111° C. LRMS (ES+) m/z 346.9 (C₁₈H₂₂N₂O₅+H requires347.10).

To a suspension ofmethyl(2S)-3-[(tert-butoxy)carbonylamino]-2-[(4-ethynylphenyl)carbonylamino]propanoate(4) (200 mg, 0.577 mmol) and2-[(tert-butoxy)carbonylamino]-N-(4-iodophenyl)acetamide (2) (476 mg,1.26 mmol) was added Et₃N (350 μL, 2.5 mmol). The solution was purgedwith a stream of N₂ for several minutes and PdCl₂(PPh₃)2 (20 mg, 0.028mmol) and CuI (10.6 mg, 0.055 mmol) were added. The reaction mixture wasstirred at ambient temperature for 22 h and then concentrated by rotaryevaporation. The crude black residue was chromatographed twice by silicagel chromatography (30:1 CH₂Cl₂/MeOH) to give 285 mg (83%) ofmethyl(2S)-3-[(tert-butoxy)carbonylamino]-2-{4-[2-(4-{2-[(tert-butoxy)carbonylamino]acetylamino}phenyl)ethynyl]phenyl}carbonylamino)propanoate(5) as a yellow foam.

To a solution of hydroxylamine hydrochloride (98 mg, 1.41 mmol) in MeOH(1.3 mL) at 0° C. was added 25 wt % NaOMe (460 mg, 2.13 mmol). Thesolution was stirred at 0° C. for 15 min and then charged with asolution ofmethyl(2S)-3-[(tert-butoxy)carbonylamino]-2-{4-[2-(4-{2-[(tert-butoxy)carbonylamino]acetylamino}phenyl)ethynyl]phenyl}carbonylamino)propanoate(4) (279 mg, 0.469 mmol) in THF (1.5 mL) and MeOH (0.6 mL). The reactionwas stirred at 0° C. for 30 min and at room temperature for 2.5 h. Thereaction mixture was diluted with 4:1 CHCl₃/iPrOH (50 ml) and washedwith 0.1 M HCl (30 mL). The layers were separated and the aqueous layerextracted once more with 4:1 CHCl₃/iPrOH (30 ml). The organic layerswere combined, dried over Na₂SO₄, filtered and concentrated. The cruderesidue was suspended in 10:1 CH₂Cl₂/MeOH (4 mL), filtered, and washedwith 50:1 CH₂Cl₂/MeOH (2 mL) and Et₂O (10 mL) to afford 180 mg (64%) ofN-(4-{2-[4-(N-{1-(N-hydroxycarbamoyl)(1S)-2-[(tert-butoxy)carbonylamino]ethyl)carbamoyl)phenyl]ethynyl}phenyl)-2-[(tert-butoxy)carbonylamino]acetamide (6) as awhite powder.

To an oven-dried flask containingN-(4-{2-[4-(N-(1-(N-hydroxycarbamoyl)(1S)-2-[(tert-butoxy)carbonylamino]ethyl}carbamoyl)phenyl]ethynyl}phenyl)-2-[(tert-butoxy)carbonylamino]acetamide(6) (130 mg, 0.218 mmol) was added 1:1 TFA/CH₂Cl₂ (2.5 mL). Theresulting pink solution was stirred for 2 h and concentrated to give apink gum. The crude residue was rinsed with CH₂Cl₂ (4 mL), concentratedby rotary evaporation and dissolved in THF (2 mL) and MeOH (0.4 mL). Asolution of 4 M HCl in dioxane (200 μL) was added and the resultingprecipitate filtered and washed with Et₂O (10 mL) to afford 90 mg of4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamideas a pale tan powder.Reaction of Iodoaniline with Bromoacetyl Bromide

Bromoacetyl bromide (175 L, μ2.00 mmol) was added dropwise over 5minutes to a solution of 4-iodoaniline (438 mg, 2.00 mmol) and Et₃N (280μL, 2.00 mmol) in benzene (5 mL). The reaction was stirred 1 hour,treated with morpholine (1.0 mL, 11.5 mmol) and stirred overnight. Thereaction mixture was diluted with EtOAc (200 mL), washed with aqueous0.1 M KOH (50 mL), H₂O (50 mL), dried over MgSO₄ and concentrated togive a yellow oil. Purification by silica gel chromatography (100:1CH₂Cl₂/MeOH) afforded 630 mg (91%) ofN-(4-iodophenyl)-2-morpholin-4-ylacetamide as a waxy tan solid. Thisproduct was converted to analogues in a similar manner as Example 14.

Example A Preparation of4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester

Reagent MW EQ g/ml mmol H-DAP(Boc)-OMe (1) 254 1.05 5.93 g 23.34-Iodo-benzoic acid 248 1.0 5.49 g 22.2 HOAT 136.1 1.02 3.08 g 22.6 EDC191.71 1.02 4.33 g 22.6 DIEA 129.25 2.5  9.7 ml 55.1 DMF   85 ml

DIEA (9.7 ml, 55.1 mmol) was added to a stirred solution of4-iodo-benzoic acid (5.49 g, 22.2 mmol), HOAT (3.08 g, 22.6 mmol), EDC(4.33 g, 22.6 mmol) in DMF (85 ml). After 2 min., the H-DAP(Boc)-OMe (1)was added in one portion. After 12 hours, the reaction was foundcomplete by LCMS. The reaction was diluted with EtOAc/hexane (1:1) (500ml). The organic phase was washed with 1N HCl (2×80 ml), 1N NaOH (2×80ml), water (2×80 ml), sat. brine (80 ml), dried with Na₂SO₄, filteredand concentrated under reduced pressure to give crude product. Theresidue was filtered through a filter plug of silica eluting withEtOAc/hexane (1:1). The fractions with product were evaporated to give9.3 g of product(3-tert-Butoxycarbonylamino-2-(4-iodo-benzoylamino)-propionic acidmethyl ester) in 93% yield. This product was converted to analogues in asimilar manner as the aforementioned Examples.

Example 15N-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxypropyl)(4-{2-[4-morpholin-4-ylmethyl)phenyl]ethynyl}phenyl)carboxamide(5)

Preparation of(2S,3R)-2-[4-(4-formyl-phenylethynyl)-benzoylamino]-3-hydroxy-butyricacid methyl ester (3)

Reagent MW Eq. g/ml mmol Ethynylbenzene (1) 261.27 1.0 0.745 g 2.854-Iodobenzaldehyde (2) 232.00 1.4 0.902 g 3.89 PdCl₂(PPh₃)₂ 701.89 0.030.070 g 0.10 CuI 190.44 0.06 0.034 g 0.18 Et₃N 101.19 2.3  0.90 mL 6.5THF   50 mL

A solution of alkyne 1 (745 mg, 2.85 mmol), 4-iodobenzaldehyde 2 (902mg, 3.89 mmol), and Et₃N (900 μL, 6.5 mmol) in THF (50 mL) was purgedwith a stream of N₂ for two minutes and then treated with PdCl₂(PPh₃2(70 mg, 0.10 mmol) and CuI (34 mg, 0.18 mmol). The reaction mixture wasstirred 40 h, concentrated by rotary evaporation and purified by silicagel chromatography (40:1 DCM/MeOH) to give 0.833 g (80% yield) of(2S,3R)-2-[4-(4-formyl-phenylethynyl)-benzoylamino]-3-hydroxy-butyricacid methyl ester 3 as a pale yellow powder, mp=143-144° C. R_(f)=0.3(25:1 DCM/MeOH); LRMS (ES+) m/z 366.1 (C₂₁H₁₉NO₅+H requires 366.13);HPLC (300 nm, 47 min) 15.3 min.

Preparation of(2S,3R)-3-Hydroxy-2-[4-(4-morpholin-4-ylmethyl-phenylethynyl)-benzoylamino]-butyricacid methyl ester (4)

Reagent MW Eq. g/ml mmol Tolanylaldehyde (3) 365.38 1.0 0.822 g 2.25Morpholine 87.12 1.3 0.260 mL 2.97 NaBH(OAc)₃ 211.94 1.4 0.670 g 3.16THF   15 ml

Sodium triacetoxyborohydride (0.670 g, 3.16 mmol) was added to asolution of benzaldehyde 3 (0.822 g, 2.25 mmol) and morpholine (260 μL,2.97 mmol) in THF (15 mL) under N₂ atmosphere and the reaction monitoredby TLC (25:1 DCM/MeOH, R_(f)=0.2). After stirring 4 h, the reactionmixture was quenched with saturated NaHCO₃ (150 mL), extracted withEtOAc (3×100 mL), dried over MgSO₄, filtered and concentrated to give ayellow syrup. Purification by silica gel chromatography (35:1 DCM/MeOH)afforded 0.844 g (86% yield) of 4 as a sticky white foam.

Preparation of(2S,3R)-N-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-(4-morpholin-4-ylmethyl-phenylethynyl)-benzamide(5)

Reagent MW Eq. g/ml mmol Methyl ester (4) 436.50 1.0 0.829 g 1.90NH₂OH—HCl 69.49 3.0 0.400 g 5.76 NaOMe (25 wt %) 54.02 4.5 1.860 g 8.60MeOH    8 mL THF    3 mL

Sodium methoxide (25 wt % in MeOH, 1.860 g, 8.60 mmol) was added to astirred solution of hydroxylamine hydrochloride (400 mg, 5.76 mmol) inanhydrous MeOH (5 mL) at 0° C. under N₂ atmosphere. After stirring 20min, a solution of methyl ester 4 (829 mg, 1.90 mmol) in 1:1 MeOH/THF (6mL) was added and the reaction mixture stirred at 0° C. for 1 h and atroom temperature for 4 h. The reaction was quenched with 1.0 M HCl (6mL), concentrated by rotary evaporation to remove organic solvents, anddiluted with DMSO (4 mL). Analytical RP-HPLC (C₁₈ column, CH₃CN gradient5-35%, 0.1% TFA, UV analysis 300 nm, 16 min) indicated a purity of 85%for the crude product mixture. Purification by preparative RP-HPLC andlyophilization of the collected fractions gave 701 mg (81%) of 5 as afluffy white solid. LRMS (ES+) m/z 438.1 (C₂₄H₂₇N₃O₅+H requires 438.20);RP-HPLC (300 nm, 16 min run) 8.7 min.

Resin Procedures for Synthesizing Tolanyl Hydroxamates

Example 16 Synthesis of4-[(4-{[(benzylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide

1. Coupling to Fmoc Hydroxylamine Resin

The resin was pre-swelled by adding DCM and shaking for 30 min. Theresin was drained, 20% piperdine was added in DMF, the resin was shaken1.25 hours, and finally drained and washed in 2×DMF and 2×DCM. Afterdraining completely, 20% piperdine in DMF was added to attain cleavagein 1.25 hours. The resin was washed 4×DMF, 4×DCM and drained completely.In a separate flask, the amino acid (Fmoc-Thr tBu-OH, or Fmoc-DAPBoc-OH, 4 eq) was mixed, HATU (4 eq), DMF (60 ml) and Hunig's (8 eq)base were added and stirred for 2-3 min. The mixture was added to theresin and shaken 20-24 hours. Subsequently, the resin was drained andrun with a standard wash (1×DCM, 4×DMF and 4×DCM). The Fmoc was removedfrom the amino acid by adding 20% piperdine in DMF and shaken 1.25hours, drained, and given the standard wash (1×DCM, 4×DMF and 4×DCM).

2. Coupling of 4-iodobenzoic Acid to Amino Acid Resin

A mixture of 4-iodobenzoic acid (4 eq), HBTU (4 eq), DMF (60 ml) wasshaken for several minutes. Hünig's base (8 eq) was subsequently addedand the mixture was shaken further for 2-3 min. The pre-activatedmixture was then added to the prepared Thr or DAP resin (Fmoc removed,7.5 g, 5.775 mmol). The reaction is shaken 12-16 hours followed by thestandard wash (1×DCM, 4×DMF and 4×DCM).

3. Alkyne Coupling on Resin

To the 4-iodobenzoic resin (4 g, 3.08 mmol) was added4-aminophenylacetylene (3 eq), Pd(PPh₃)₂Cl₂ (0.04 eq), CuI (0.08 eq) andTHF (urged with Argon). After mixing for 1 min., TEA (4.5 eq) was addedand the reaction was shaken 12 hours at RT under argon.

4. Aniline Coupling with Bromoacetyl Chloride on Resin

To aniline resin (4 g, 3.08 mmol) was added DCM (30 ml) lutidine (10 eq)and shaken for 1 min. Bromoacetyl chloride (8 eq) in DCM (5 ml) wasadded slowly. After the addition, the slurry was shaken for 1.5 to 1.75hours. Subsequent draining and a wash with 2×DCM, 4×DMF and 4×DCM wasthen performed.

5. Displacement with Amines on Resin

To the bromoacetyl resin (125 mg), was added NMP (1.5 ml) followed byamine (0.2 g or ml, ie excess) and the slurry was shaken for 12-16 hoursat RT. To neutralize the salt, TEA was added. The imidazole was heatedat 38° C. for 24 h (in the case of anilines, they were heated at 38° C.for 48 h). The reaction mixture was drained and washed 4×DMF and 4×DCM.

6. Cleavage from Resin and Deprotection of Thr tBu and DAP Boc

The resin (125 mg) was soaked in TFA/water (80:20 v/v) (1.5 ml) at RTfor 45 min. Upon cleavage the solution was collected and the resin waswashed with more TFA/water mixture (0.75 ml). To the TFA/productsolution was added acetonitrile/water solution (1:1 v/v, 10 ml) and purewater (2.5 ml). The mixture was frozen in liquid nitrogen for ˜15 minand lyophilized. The dry residue was dissolved in the acetonitrile/watersolution (1:1 v/v, 10 ml) again followed by addition of 1M aq. HCl (1.2eq per basic nitrogen), frozen, and lyophilized to a powder.

Synthesis of 3′-Nitro-Tolan Threonine Hydroxamic Acid

Example 17(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-phenylethynyl)-benzamide

Preparation of(1S,2R)-N-(2-tert-butoxy-1-hydroxycarbamoyl-propyl)-4-ethynyl-benzamideon hydroxylamine 2-chlorotrityl resin (3)

Reagent MW Eq. g/mL mmol Fmoc-threonine/resin (1) 0.70 mmol/g 1.0 0.522g 0.365 4-Ethynylbenzoic acid (2) 146.14 3.0 0.160 g 1.10 DIC 126.20 4.90.28 mL 1.79 HOBt 135.13 3.0 0.148 g 1.10 DIEA 129.25 6.3 0.40 mL 2.30DCM 1.0 mL DMF 3.0 mL

The resin 1 (0.522 g, 0.365 mmol, 0.70 mmol/g) was swelled in DCM (5 mL)for 2 h and drained. The resin was treated with 20% piperidine in DMF (6mL) for 1 hour, washed with DMF (4×6 mL) and DCM (4×6 mL) and drainedcompletely. In a separate flask, 4-ethynylbenzoic acid 2 (0.160 g, 1.10mmol), DIC (0.280 mL, 1.79 mmol), HOBt (0.148 g, 1.10 mmol) and DIEA(0.4 mL, 2.30 mmol) were dissolved in DCM (1 mL) and DMF (4 mL), stirred15 min and added to the resin. After shaking for 36 h, the mixture wasdrained, washed with DMF (4×6 mL) and DCM (4×6 mL) and dried in vacuo togive 0.495 g of a yellow resin.

Preparation of(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-phenylethynyl)-benzamide(5)

Reagent MW Eq. g/mL mmol Alkyne on resin (3) 0.70 mmol/g 1.0 100 mg0.070 1-Iodo-3-nitrobenzene (4) 249.01 5.0 87.1 mg 0.350 PdCl₂(PPh₃)₂701.89 0.2 10.0 mg 0.014 CuI 190.44 0.5 7.0 mg 0.036 Et₃N 101.19 15 150μL 1.10 DMF 1.5 mL

Resin 3 (100 mg, 0.070 mmol) was swelled in DCM (2 mL) for 1 h anddrained. A solution of 1-iodo-3-nitrobenzene 4 (87.1 mg, 0.350 mmol) andEt₃N (150 μL, 1.10 mmol) in DMF (1.5 mL) was purged with a stream of N₂bubbles for two minutes and added to the resin. After mixing for 5 min,PdCl₂(PPh₃)₂ (10.0 mg, 0.014 mmol) and CuI (7.0 mg, 0.036 mmol) wereadded and the mixture shaken for 26 h. The resin was drained, washedwith DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10% TFA/DCM (1.5 mL)for 20 min. The solution was collected and the resin was rinsed withadditional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined,treated with neat TFA (2.0 mL), stirred for 1 h at rt and concentratedby rotary evaporation to give a crude brown residue. Purification byRP-HPLC (C₁₈ column, CH₃CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm,28 min) and lyophilization of the collected fractions afforded 6.0 mg(22% yield) of(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-phenylethynyl)-benzamideas a white foam. LRMS (ES+) m/z 384.2 (C₁₉H₁₇N₃O₆+H requires 384.15);RP-HPLC (300 nm, 28 min run) 15.2 min.

Synthesis of 4′-Trifluoromethoxy-Tolan Dap Hydroxamic Acid

Example 18(1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamide(5)

Preparation of(1S)-N-(2-(Boc)-amino-1-hydroxycarbamoyl-ethyl)-4-ethynyl-benz-amide onhydroxylamine 2-chlorotrityl resin (3)

Reagent MW Eq. g/mL mmol Fmoc-Dap/resin (1) 0.70 mmol/g 1.0 1.330 g0.931 4-Ethynylbenzoic acid (2) 146.14 3.0 0.408 g 2.793 DIC 126.20 4.80.70 mL 4.470 HOBt 135.13 3.0 0.377 g 2.793 DIEA 129.25 6.2 1.0 mL 5.7DCM 10.0 mL DMF 2.0 mL

The resin 1 (1.330 g, 0.931 mmol, 0.70 mmol/g) was swelled in DCM (15mL) for 2 h and drained. The resin was treated with 20% piperidine inDMF (20 mL) for 1 hour, washed with DMF (3×15 mL) and DCM (3×15 mL) anddrained completely. In a separate flask, 4-ethynylbenzoic acid 2 (0.408g, 2.793 mmol), DIC (0.70 mL, 4.470 mmol), HOBt (0.377 g, 2.793 mmol)and DIEA (1.0 mL, 5.7 mmol) were dissolved in DCM (10 mL) and DMF (2mL), stirred 15 min and added to the resin. After shaking for 36 h, themixture was drained, washed with DMF (3×15 mL) and DCM (3×15 mL) anddried in vacuo to give 1.290 g of a yellow resin.

Preparation of(1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamide(5)

Reagent MW Eq. g/mL mmol Alkyne on resin (3) 0.70 mmol/g 1.0 120 mg0.084 4-CF₃O-iodobenzene (4) 287.99 4.0 96.8 mg 0.336 PdCl₂(PPh₃)₂701.89 0.3 18.0 mg 0.025 CuI 190.44 0.5 8.0 mg 0.042 Et₃N 101.19 13 150μL 1.10 DMF 2.0 mL

Resin 3 (120 mg, 0.084 mmol) was swelled in DCM (2 mL) for 1 h anddrained. A solution of 4-trifluoromethoxy)iodobenzene 4 (96.8 mg, 0.336mmol) and Et₃N (150 μL, 1.10 mmol) in DMF (2.0 mL) was purged with astream of N₂ bubbles for two minutes and added to the resin. Aftermixing for 5 min, PdCl₂(PPh₃)₂ (18.0 mg, 0.025 mmol) and CuI (8.0 mg,0.042 mmol) were added and the mixture shaken for 24 h. The resin wasdrained, washed with DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10%TFA/DCM (2.0 mL) for 20 min. The solution was collected and the resinwas rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractionswere combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt andconcentrated by rotary evaporation to give a crude brown residue.Purification by RP-HPLC (C₁₈ column, CH₃CN gradient 5-55%, 0.1% TFA, UVanalysis 300 nm, 28 min) and lyophilization of the collected fractionsafforded 9.0 mg (25% yield) of(1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamideas a white solid. LRMS (ES+) m/z 408.0 (C₁₉H₁₆F₃N₃O₄+H requires 408.11);RP-HPLC (300 nm, 28 min run) 18.0 mm.

Example 19 Synthesis ofN-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxypropyl)[4-(4-phenylbuta-1,3-diynyl)phenyl]carboxamide

Reagent MW EQ g/ml mmol Dibromovinylbenzoic acid (2) 320 1.0 5.76 g 18.0Ethynyl-benzene 102 1.4 2.57 g 25.2 Pd₂dba₃ 915 0.01  164 mg  0.18 (1%cat.) TMPP 352 0.04  253 mg  0.72 (4%) TEA 101 3.0  7.5 ml 54.0 DMF   60ml degassed with argonThe 4-2,2-Dibromo-vinyl)-benzoic acid methyl ester (2) was made by themethod of Wang Shen and Le Wang in J. Org. Chem. 1999, 64, 8873-8879.

A solution of 4-(2,2-dibromo-vinyl)-benzoic acid methyl ester (2) (5.76g, 18.0 mmol), ethynyl-benzene (2.57 g, 25.2 mmol), Pd₂ dba₃ (164 mg,0.18 mmol), tris(4-methoxyphenyl) phosphine (TMPP) (253 mg, 0.72 mmol)were dissolved in argon sparged (5 min.) DMF (60 ml). The reaction wassparged with argon for 1 min. TEA (7.5 ml, 54.0 mmol) was added to thestirred reaction mixture that was then heated under argon at 85° C. for3.5 hours. The reaction was found complete by LCMS. The reaction wascooled to rt and diluted with EtOAc/hexane (1:1) (300 ml). The organicphase was washed with 1M HCl (2×50 ml), 1M NaOH (3×50 ml), water (2×50ml), sat. brine (50 ml), dried with Na₂SO₄, filtered and concentratedunder reduced pressure to obtain 5.25 g of crude product as an oil. Theoil was treated with approximately 20 ml of a solution of 20%EtOAc/hexane that was heated to dissolve the residue. The walls of theflask were washed with the 20% EtOAc/hexane solution (5 ml) that uponcooling gave 1.45 g of pure product (31% yield) as a white solid. Thebalence of the crude reaction product was purified by flashchromatography using EtOAc (8%)/hexane as eluant. The pure fractionswere evaporated and dried in vacuo to give addition product typically25-30% addition yield.

4-(4-Phenyl-buta-1,3-diynyl)-benzoic acid methyl ester (4) was madeaccording to the method of Wang Shen and Sheela A. Thomas in Org. Lett.2000, 2(18), 2857-2860.

Preparation of 4-(4-Phenyl-buta-1,3-diynyl)-benzoic acid (5)

A 3M aq. solution of NaOH (20 ml) was added to a stirred solution ofmethyl ester 4 (1.45 g, 5.6 mmol) in MeOH (100 ml) at rt. The reactionsolution was heated to reflux for 45 min. until the reaction turnedclear. All of the starting material was gone by TLC and HPLC. Thereaction was cooled to rt and some MeOH (˜50 ml) was removed byevaporation under reduced pressure. Water (100 ml) was added to themixture. Conc. HCl was added dropwise to the stirred solution untilacidic by pH paper (pH2). The white precipitate that formed wascollected by suction filtration. The solid was washed with water (3×20ml) and hexane (2×20 ml) to give after drying 1.35 g of product acid 5in 99% yield.

Subsequent conversion of compound 5 to compound 7 was performedaccording to the method described in Example 12 for the synthesis ofN-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide(compound 5). LCMS MH+ 363.13.

Example B Synthesis ofN-[(1S)-1-aminomethyl)-2-(hydroxyamino)-2-oxoethyl]4-[4-(4-aminophenyl)buta-1,3-diynyl]benzamidePreparation of2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonylamino-propionicacid methyl ester (2)

Reagent MW EQ g/ml mmol H-DAP(Boc)-OMe 254 1.05 5.12 g 20.1 1,3-diynylbenzoic acid (1) 261.3 1.0 5.0 g 19.1 HOBT 135.1 1.05 2.72 g 20.1 EDC191.71 1.05 3.85 g 20.1 DIEA 129.25 3.0 10.5 ml 60.3 DMF 80 ml

DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of4-[4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol),HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours atrt, the reaction was found complete by LCMS. The reaction was dilutedwith EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1NNaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na₂SO₄,filtered and concentrated under reduced pressure to give crude product.The residue was filtered through a filter plug of silica eluting withEtOAc/hexane (4:1). The fractions with product were evaporated to give8.02 g of product in 91% yield.

Subsequent conversion of compound 2 to the final hydroxamic acid (forexample, Example 892) was performed according to the method described inExample 12 for the synthesis ofN-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide(compound 5).Synthesis of 4-(Buta-1,3-diynyl)-benzoic Acid (4) for Making 1,3-diynylAnalogues (Such as Example 20 Below)

Preparation of 4-(4-trimethylsilanyl-buta-1,3-diynyl)-benzoic acidmethyl ester (3)

Reagent MW Eq. g/ml mmol Methyl 4-iodobenzoate (2) 262.04 1.0 4.510 g17.2 Trimethylsilylbutadiyne (1) 122.24 2.5 5.240 g 42.8 PdCl₂(PPh₃)₂701.89 0.04 0.483 g 0.690 CuI 190.44 0.08 0.262 g 1.37 Et₃N 101.19 3.0 7.2 mL 52.0 CH₃CN   50 mL

A solution of methyl 4-iodobenzoate 2 (4.510 g, 17.2 mmol), PdCl₂(PPh₃)₂(483 mg, 0.690 mmol), and CuI (262 mg, 1.37 mmol) in CH₃CN (50 mL) wascooled to 0° C. under N₂ atmosphere in the absence of lightTriethylamine (7.2 mL, 52.0 mmol) was added, followed bytrimethylsilyl-1,3-butadiyne 1 (5.240 g, 42.8 mmol) and the reactionstirred 3 h at 0° C. and 30 h at ambient temperature. Removal of solventby rotary evaporation afforded a crude black residue that was purifiedby silica gel chromatography (95:5 hexanes/EtOAc) to give 3.450 g (79%yield) of 4-(4-trimethylsilanyl-buta-1,3-diynyl)-benzoic acid methylester 3 as a brown solid, mp=67-68° C.

Preparation of 4-(buta-1,3-diynyl)-benzoic acid (4)

Reagent MW Eq. g/ml mmol Methyl ester (3) 252.34 1.0 3.420 g 13.5 KOH56.11 4.9 3.700 g 65.9 H₂O 10 mL THF 26 mL

Potassium hydroxide (3.700 g, 65.9 mmol) was dissolved in H₂O (10 mL)and added to a solution of4-(4-trimethylsilanyl-buta-1,3-diynyl)-benzoic acid methyl ester 3(3.420 g, 13.5 mmol) in THF (26 mL) in the absence of light. Afterstirring 16 h, the reaction was quenched with 1.0 M HCl (120 mL) and theresulting precipitate was filtered, washed with 1:1 hexanes/benzene (150mL) and dried in vacuo to afford 2.100 g (91% yield, 98% pure) of4-(buta-1,3-diynyl)-benzoic acid 4 as a brown solid, mp>230° C. Althoughdiyne 4 was found to be unstable at room temperature it could be storedfor several weeks at 0° C. with only small amounts of decompositionobserved by TLC. R_(f)=0.2 (4:1 Hexanes/EtOAc); HPLC (300 nm, 28 minrun) 16.0 min; LRMS (ES+) m/z 171.0 (C₁₁H₆O₂+H requires 171.04).

Synthesis of a 3′-Nitrophenyl-Diacetylenic-Dap Hydroxamic Acid

Example 20N-(1-(N-hydroxycarbamoyl)(1S)-2-aminoethyl){4-[4-(3-nitrophenyl)buta-1,3-diynyl]phenyl}carboxamide(6)

Preparation of Fmoc-Dap(Boc)-NHOH on hydroxylamine 2-chlorotrityl resin(2)

Reagent MW Eq. g/mL mmol Hydroxylamine resin  0.77 mmol/g 1.0 3.288 g2.53 (1) Fmoc-Dap(Boc)-OH 426.47 3.0 3.175 g 7.44 HATU 380.25 3.0 2.829g 7.44 DIEA 129.25 10.0  4.3 mL 24.7 DMF   35 mL

A suspension of N-Fmoc-hydroxylamine 2-chlorotrityl resin (3.288 g, 2.53mmol, 0.77 mmol/g, Novabiochem) in DCM (40 mL) was shaken for 2 h anddrained. The resin was treated with 20% piperidine in DMF (40 mL) for 1hour, washed with DMF (2×, 40 mL), treated a second time with 20%piperidine in DMF (40 mL), washed with DMF (3×40 mL) and DCM (3×40 mL)and drained completely. In a separate flask, Fmoc-Dap(Boc)-OH (3.175 g,7.44 mmol), HATU (2.829 g, 7.44 mmol) and DIEA (4.3 mL, 24.7 mmol) weredissolved in DMF (35 mL), stirred three minutes and added to the resin.After shaking for 48 h, the mixture was drained, washed with DMF (4×40mL) and DCM (4×40 mL) and dried in vacuo to give 3.530 g of a yellowresin.

Preparation of(S)-N-(2-N-Fmoc-amino-1-hydroxycarbamoyl-ethyl)-4-buta-1,3-diynyl-benzamideon hydroxylamine 2-chlorotrityl resin (4)

Reagent MW Eq. g/mL mmol Fmoc-Dap(Boc)/resin (2)  0.71 mmol/g 1.0 3.530g 2.53 Butadiynyl benzoic acid (3) 170.16 2.5 1.076 g 6.32 EDCI 191.713.0 1.457 g 7.60 HOBt 135.13 3.0 1.048 g 7.75 DIBA 129.25 5.0  2.2 ml12.6 DCM   25 ml DMF    5 ml

The resin 2 (3.530 g, 2.53 mmol, 0.71 mmol/g) was swelled in DCM (40 mL)for 2 h and drained. The resin was treated with 20% piperidine in DMF(40 mL) for 1 hour, washed with DMF (4×40 mL) and DCM (4×40 mL) anddrained completely. In a separate flask, 4-buta-1,3-diynyl-benzoic acid3 (1.076 g, 6.32 mmol), EDCI (1.457 g, 7.60 mmol), HOBt (1.048 g, 7.75mmol) and DIEA (2.2 mL, 12.6 mmol) were dissolved in DCM (25 mL) and DMF(5 mL), stirred 45 min and added to the resin. After shaking for 48 h,the mixture was drained, washed with DMF (4×40 mL) and DCM (4×40 mL) anddried in vacuo to give 3.35 g of a pale brown resin.

Preparation of(S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-[4-(3-nitro-phenyl)-buta-1,3-diynyl]-benzamide(6)

Reagent MW Eq. g/mL mmol Diacetylene on resin (4) 0.77 mmol/g 1.0 176 mg0.135 1-Iodo-3-nitrobenzene 249.01 3.5 118 mg 0.474 (5) PdCl₂(PPh₃)₂701.89 0.07 6.0 mg 0.009 CuI 190.44 0.38 10.0 mg 0.052 Et₃N 101.19 10.6200 μL 1.43 DMF 3.0 mL

Resin 4 (176 mg, 0.135 mmol) was swelled in DCM (3 mL) for 1 h anddrained. A solution of 1-iodo-3-nitrobenzene 5 (118 mg, 0.474 mmol) andEt₃N (200 μL, 1.43 mmol) in DMF (3.0 mL) was purged with a stream of N₂bubbles for two minutes and added to the resin. After mixing for 5 min,PdCl₂(Ph₃)₂ (6.0 mg, 0.009 mmol) and CuI (10.0 mg, 0.052 mmol) wereadded and the mixture shaken for 36 h. The resin was drained, washedwith DMF (4×3 mL), DCM (4×3 mL) and cleaved with 10% TFA/DCM (2 mL) for20 min. The solution was collected and the resin was rinsed withadditional 10% TFA/DCM (2 mL). The cleavage fractions were combined,treated with neat TFA (4.0 mL), stirred for 1 h at rt and concentratedby rotary evaporation to give a crude brown residue. Purification byRP-HPLC (C₁₈ column, CH₃CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm,30 min) and lyophilization of the collected fractions afforded 12.0 mg(22%) of 470 as a white solid. LRMS (ES+) m/z 392.9 (C₂₀H₁₆N₄O₅+Hrequires 393.11); RP-HPLC (300 nm, 30 min run) 14.9 min.

Synthesis of 4′-Benzamide Diacetylene Dap Hydroxamic Acid

Example 21N-((2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4-(2-amino-ethylcarbamoyl)phenyl]-buta-1,3-diynyl}-benzamide (3)

Preparation ofN-(2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide(3)

Reagent MW Eq. g/mL mmol Alkyne on resin (1) 0.77 mmol/g 1.0 145 mg0.111 4-Ethynylbenzamide (2) 430.54 2.6 124 mg 0.288 PdCl₂(PPh₃)₂ 701.890.3 21 mg 0.030 CuI 190.44 1.0 22 mg 0.110 Et₃N 101.19 6.5 100 μL 0.72DMF 2.0 mL

Resin 1 (145 mg, 0.111 mmol) was swelled in DCM (2 mL) for 1 h anddrained. A solution of 4-ethynylbenzamide 2 (124 mg, 0.288 mmol) andEt₃N (100 μL, 0.72 mmol) in DMF (2.0 mL) was added and the resinagitated for 5 min. A mixture of PdCl₂(PPh₃)₂ (21 mg, 0.030 mmol) andCuI (22 mg, 0.110 mmol) was added and the resin was agitated for 60 h.The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mL) andcleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collectedand the resin was rinsed with additional 10% TFA/DCM (1.0 mL). Thecleavage fractions were combined, treated with neat TFA (2.0 mL),stirred for 1 h at rt and concentrated by rotary evaporation to give acrude brown residue. Purification by RP-HPLC (C₁₈ column, CH₃CN gradient5-55%, 0.1% TFA, UV analysis 300 nm, 26 min) and lyophilization of thecollected fractions afforded 2.6 mg (5% yield) ofN-((2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide.LRMS (ES+) m/z 434.0 (C₂₃H₂₃N₅O₄+H requires 434.19); RP-HPLC (300 nm, 26min run) 15.3 min.Synthesis of N-[4-Butadiynyl-benzoyl]-Thr(tBu) on Resin (Continued toMake Examples 22 and 23)

Preparation of (2S,3R)-2-N-Fmoc-amino-3-tert-butoxy-N-hydroxy-butyramideon hydroxylamine 2-chlorotrityl resin (2)

Reagent MW Eq. g/mL mmol Hydroxylamine resin (1)  0.77 mmol/g 1.0 3.188g 2.45 Fmoc-Thr(tBu)-OH 397.50 3.0 2.927 g 7.36 HATU 380.25 3.0 2.798 g7.36 DIBA 129.25 10.0  4.3 mL 24.6 DMF   40 mL

A suspension of N-Fmoc-hydroxylamine 2-chlorotrityl resin (3.188 g, 2.45mmol, 0.77 mmol/g, Novabiochem) in DCM (40 mL) was shaken for 2 h anddrained. The resin was treated with 20% piperidine in DMF (40 mL) for 1hour, washed with DMF (2×40 mL), treated a second time with 20%piperidine in DMF (40 mL), washed with DMF (3×40 mL) and DCM (3×40 mL)and drained completely. In a separate flask, Fmoc-Thr(tBu)-OH (2.927 g,7.36 mmol), HATU (2.798 g, 7.36 mmol) and DIEA (4.3 mL, 24.6 mmol) weredissolved in DMF (40 mL), stirred three minutes and added to the resin.After shaking for 24 h, the mixture was drained, washed with DMF (4×40mL) and DCM (4×40 mL) and dried in vacuo to give 3.500 g of a yellowresin.

Preparation of4-buta-1,3-diynyl-N-(2-tert-butoxy-1-hydroxycarbamoyl-propyl)-benzamideon hydroxylamine 2-chlorotrityl resin (4)

Reagent MW Eq. g/mL mmol Fmoc-threonine/resin (2) 0.77 mmol/g 1.0 2.030g 1.56 Butadiynyl benzoic acid (3) 170.16 2.3 0.617 g 3.63 EDCI 191.712.8 0.834 g 4.35 HOBt 135.13 2.8 0.588 g 4.35 DIEA 129.25 3.7  1.0 mL5.7 DCM   15 mL DMF    4 mL

The resin 2 (2.030 g, 1.56 mmol, 0.77 mmol/g) was swelled in DCM (20 mL)for 2 h and drained. The resin was treated with 20% piperidine in DMF(20 mL) for 1 hour, washed with DMF (4×20 mL) and DCM (4×20 mL) anddrained completely. In a separate flask, 4-buta-1,3-diynyl-benzoic acid3 (0.617 g, 3.63 mmol), EDCI (0.834 g, 4.35 mmol), HOBt (0.588 g, 4.35mmol) and DIEA (1.0 mL, 5.7 mmol) were dissolved in DCM (15 mL) and DMF(4 mL), stirred 45 min and added to the resin. After shaking for 36 h,the mixture was drained, washed with DMF (4×20 mL) and DCM (4×20 mL) anddried in vacuo to give 1.900 g of a pale brown resin.

Synthesis of Diacetylenic Threonine Hydroxamic Acids

Example 22(2S,3R)-4-[4-(3-aminomethyl-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide(3)

Reagent MW Eq. g/mL mmol Diacetylene on resin (1)  0.77 mmol/g 1.0 100mg 0.077 3-Iodobenzylamine HCl 269.51 4.0 83.0 mg 0.308 (2) PdCl₂(PPh₃)₂701.89 0.2 11.0 mg 0.016 Cul 190.44 0.5 7.0 mg 0.037 Et₃N 101.19 23 250μL 1.80 DMF 1.5 mL

Resin 1 (obtained from previous synthesis) (100 mg, 0.077 mmol) wasswelled in DCM (2 mL) for 1 h and drained. A solution of3-iodobenzylamine hydrochloride 2 (83.0 mg, 0.308 mmol) and Et₃N (250μL, 1.80 mmol) in DMF (1.5 mL) was purged with a stream of N₂ bubblesfor two minutes and added to the resin. After mixing for 5 min,PdCl₂(PPh₃)₂ (11.0 mg, 0.016 mmol) and CuI (7.0 mg, 0.037 mmol) wereadded and the mixture shaken for 36 h. The resin was drained, washedwith DMF (4×2 mL), DCM (4×2 mL) and cleaved with 10% TFA/DCM (1.5 mL)for 20 min. The solution was collected and the resin was rinsed withadditional 10% TFA/DCM (1.5 mL). The cleavage fractions were combined,treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentratedby rotary evaporation to give a crude brown residue. Purification byRP-HPLC (C₁₈ column, CH₃CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm,28 min) and lyophilization of the collected fractions afforded 4.3 mg(14%) of(2S,3R)-4-[4-(3-aminomethyl-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamideas a white solid. LRMS (ES+) m/z 392.0 (C H₂₁N₃O₄+H requires 392.15);RP-HPLC (300 nm, 28 min run) 10.0 min.

Synthesis of Diacetylenic Benzylamine Analogues

Example 23(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-[4-(4-morpholin-4-ylmethyl-phenyl)-buta-1,3-diynyl]-benzamide(4)

Preparation of Threonine Diacetylenic Benzaldehyde on Resin (3)

Reagent MW Eq. g/mL mmol Diacetylene on resin (1)  0.77 mmol/g 1.0 1.00g 0.770 4-Iodobenzaldehyde 232.00 4.0 715 mg 3.081 PdCl₂(PPh₃)₂ 701.890.07 40.0 mg 0.057 CuI 190.44 0.13 19.0 mg 0.100 Et₃N 101.19 9.3 1.00 mL7.17 DMF 20.0 mL

Resin 1 (1.00 g, 0.77 mmol) was pre-swelled in DCM (25 mL) for 14 h anddrained. A solution of 4-iodobenzaldehyde 2 (715 mg, 3.08 mmol) and Et₃N(1.00 mL, 7.17 mmol) in DMF (20 mL) was purged with N₂ for two minutesand added to the resin. After mixing for 5 min, PdCl₂(Ph₃)₂ (49.0 mg,0.057 mmol) and CuI (19.0 mg, 0.100 mmol) were added and the reactionshaken for 48 h. The resin was drained, washed with DMF (4×20 mL), DCM(4×20 mL) and dried in vacuo to give 1.100 g of a dark yellow resin.

Preparation of(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-[4-(4-morpholin-4-ylmethyl-phenyl)buta-1,3-diynyl]-benzamide(4)

Reagent MW Eq. mg/μl mmol Benzaldehyde on resin  0.77 mmol/g 1.0 188 mg0.141 (3) Morpholine  87.12 6.0 75 μL 0.860 NaCNBH₃  62.84 4.5 40 mg0.637 Trimethyl orthoformate 106.12 6.5 100 μL 0.914 Acetic acid  60.0512.3 100 μL 1.750 THF 3.0 mL MeOH 1.0 mL

A solution of morpholine (75 μL, 0.860 mmol) and trimethyl orthoformate(100 μL, 0.914 mmol) in THF (3.0 mL) was added to a Teflon-linedscrew-capped vial containing the resin-bound diacetylenic benzaldehyde3. The resin was agitated for 10 min, treated successively with aceticacid (100 μL, 1.75 mmol) and a solution of NaCNBH₃ (40.0 mg, 0.637 mmol)in MeOH (1.0 mL) and shaken for 44 h. The resin was filtered, washedwith DMF (3×3 mL) and DCM (3×3 mL) and drained. Cleavage from the resinwas achieved by treatment with 10% TFA/DCM (2.0 mL) and shaking 20 min.The solution was collected and the resin was rinsed with additional 10%TFA/DCM (2.0 mL). The cleavage fractions were combined, treated withneat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotaryevaporation to give a crude yellow residue. Purification by RP-HPLC (C₁₈column, CH₃CN gradient 5-35%, 0.1% TFA, UV analysis 300 nm, 18 min) andlyophilization of the collected fractions afforded 19.0 mg (29%) of 472as a fluffy yellow solid. LRMS (ES+) m/z 462.0 (C₂₆H₂₇N₃O₅+H requires462.10); HPLC (300 nm, 18 min run) 10.3 min.

Synthesis of 4′-Benzamide Diacetylene Threonine Hydroxamic Acid

Example 24(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide(5)

Preparation of N-(2-trityl-amino-ethyl)-4-ethynyl-benzamide (3)

Reagent MW Eq. g/mL mmol 4-Ethynylbenzoic acid (1) 146.14 1.0 0.292 g2.00 N-Trityl ethylenediamine 302.41 1.3 0.810 g 2.67 EDCI 191.71 1.00.382 g 2.00 HOBt 135.13 3.0 0.270 g 2.00 DIEA 129.25 4.0 1.40 mL 8.00DMF 10.0 mL

To a solution of 4-ethynylbenzoic acid 1 (292 mg, 2.00 mmol), EDCI (382mg, 2.00 mmol), and HOBt (270 mg, 2.00 mmol) in DMF (10 mL) was addedN-trityl ethylenediamine 2 (810 mg, 2.67 mmol) and DIEA (1.4 mL, 8.0mmol). The reaction mixture was stirred 24 h, diluted with EtOAc (200mL), washed with 0.5 M HCl (60 mL), saturated NaHCO₃ (2×60 mL), H₂O(4×60 mL), dried over MgSO₄ and concentrated to give 836 mg (97% yield)of N-(2-trityl-amino-ethyl)-4-ethynyl-benzamide 3 as a white solid, mp50-51° C. R_(f)=0.40 (1:1 Hexanes/EtOAc).

Preparation of(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide(5)

Reagent MW Eq. g/mL mmol Alkyne on resin (4) 0.77 mmol/g 1.00 150 mg0.116 4-Ethynylbenzamide (3) 430.54 3.00 151 mg 0.350 PdCl₂(PPh₃)₂701.89 0.25 21 mg 0.030 CuI 190.44 1.25 28 mg 0.147 Et₃N 101.19 9.50 150μL 1.10 DMF 2.0 mL

Resin 4 (150 mg, 0.116 mmol) was swelled in DCM (2 mL) for 1 h anddrained. A solution of 4-ethynylbenzamide 3 (151 mg, 0.350 mmol) andEt₃N (150 μL, 1.10 mmol) in DMF (2.0 mL) was added and the resinagitated for 5 min. A mixture of PdCl₂(PPh₃)₂ (21 mg, 0.030 mmol) andCuI (28 mg, 0.147 mmol) was added and the resin was agitated for 60 h.The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mL) andcleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collectedand the resin was rinsed with additional 10% TFA/DCM (1.0 mL). Thecleavage fractions were combined, treated with neat TFA (2.0 mL),stirred for 1 h at rt and concentrated by rotary evaporation to give acrude brown residue. Purification by RP-HPLC (C₁₈ column, CH₃CN gradient5-65%, 0.1% TFA, UV analysis 300 nm, 26 min) and lyophilization of thecollected fractions afforded 2.0 mg (4% yield) of(1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide.LRMS (ES+) m/z 449.1 (C₂₄H₂₄N₄O₅+H requires 449.18); RP-HPLC (300 nm, 26min run) 17.0 min.

Synthesis of 3′-Pyridine Diacetylene Threonine Hydroxamic Acid

Example 25N-((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3-yl-buta-1,3-diynyl)-benzamide(3)

Preparation ofN-(2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3-yl-buta-1,3-diynyl)-benzamide(3)

Reagent MW Eq. g/mL mmol Alkyne on resin (1) 0.77 mmol/g 1.0 142 mg0.109 3-Ethynylpyridine (2) 103.12 3.4 38 mg 0.368 PdCl₂(PPh₃)₂ 701.890.3 22 mg 0.031 CuI 190.44 1.2 25 mg 0.131 Et₃N 101.19 13 200 μL 1.40DMF 2.0 mL

Resin 1 (142 mg, 0.109 mmol) was swelled in DCM (2 mL) for 1 h anddrained. A solution of 3-ethynylpyridine 2 (38 mg, 0.368 mmol) and Et₃N(200 μL 1.4 mmol) in DMF (2 mL) was added and the resin agitated for 5min. A mixture of PdCl₂(PPh₃)₂ (22 mg, 0.031 mmol) and CuI (25 mg, 0.131mmol) was added and the resin was agitated for 72 h. The resin wasdrained, washed with DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10%TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resinwas rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractionswere combined, treated with neat TFA (2.0 mL), stirred for 1 h at rt andconcentrated by rotary evaporation to give a crude brown residue.Purification by RP-HPLC (C₁₈ column, CH₃CN gradient 5-65%, 0.1% TFA, UVanalysis 300 nm, 24 min) and lyophilization of the collected fractionsafforded 4.4 mg (11% yield) ofN-(2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3-yl-buta-1,3-diynyl)-benzamide.LRMS (ES+) m/z 364.0 (C₂₀H₁₇N₃O₄+H requires 364.13); RP-HPLC (300 nm, 24min run) 11.2 min.

Example 26 Synthesis of N-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxypropyl){4-[4-(6-morpholin-4-yl(3-pyridyl))buta-1,3-diynyl]phenyl}carboxamide(5)

Reagent MW EQ g/ml mmol Dibromovinylbenzoic acid (1) 320 1.0 9.6 g 30.02-Chloro-5-ethynyl-pyridine 138 1.3 5.43 g 39.0 Pd₂dba₃ 915 0.01 274 mg 0.3 (1% cat.) TMPP 352 0.04 422 mg 1.2 (4%) TEA 101 3.0 12.5 ml 90.0DMF 90 ml degassed with argon

Preparation of 4-[4-(6-Chloro-pyridin-3-yl)buta-1,3-diynyl]-benzoic acidmethyl ester

4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid was madeaccording to the method of Wang Shen and Sheela A. Thomas in Org. Lett.2000, 2(18), 2857-2860.

A solution of 4-2,2-dibromo-vinyl)-benzoic acid methyl ester (1) (9.6 g,30.0 mmol), ethynyl-pyridine (2) (5.43 g, 39.0 mmol), Pd₂ dba₃ (274 mg,0.3 mmol), tris(4-methoxyphenyl) phosphine (TMPP) (422 mg, 1.2 mmol)were dissolved in argon sparged (5 min.) DMF (60 ml). The reaction wassparged with argon for 1 min. TEA (12.5 ml, 90.0 mmol) was added to thestirred reaction mixture that was then heated under argon at 85° C. for3 hours. The reaction was found complete by LCMS. The reaction wascooled to rt and diluted with EtOAc/hexane (1:1) (500 ml). The organicphase was washed with 1M NaOH (2×80 ml), water (2×80 ml), sat. brine (80ml), dried with Na₂SO₄, filtered and concentrated under reduced pressureto give crude product. The residue was filtered through a filter plug ofsilica eluting with EtOAc/hexane (1:1). The fractions with product wereevaporated to give 9.06 g of product in good purity (˜96% pure). Thematerial was taken on without further purification.

Preparation of 4-[4-(6-Chloro-pyridin-3-yl)buta-1,3-diynyl]-benzoic acid(3)

A 6M aq. solution of NaOH (15 ml) was added to a stirred solution of4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester.(9.06 g, 30 mmol) in MeOH (350 ml) at rt. The reaction solution washeated to reflux for 3 hours. The reaction stayed a mixture and did notturn clear. HPLC and LCMS indicated that the reaction was forming sideproducts. The reaction was cooled to rt and some MeOH (˜200 ml) wasremoved by evaporation under reduced pressure. Water (400 ml) was addedto the mixture. Conc. HCl was added dropwise to the stirred solutionuntil acidic by pH paper (pH2). The yellow precipitate that formed wascollected by suction filtration. The solid was washed with water (3×20ml) and hexane (2×20 ml) to give the crude product. HPLC indicated thatthere was approximately 40% product in the mixture. The crude reactionproduct was purified by flash chromatography using EtOAc (8-10%)/hexaneas eluant. The pure fractions were evaporated and dried in vacuo to give4.2 g of product 3 in 50% yield.

Preparation of[4-[4-(6-chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoyl]-HN-Thr(OtBu)-hydroxamicacid trityl resin (4)

4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid (3) wascoupled to a tert-butyl protected threonine pre-loaded on hydroxylamine2-chlorotrityl resin following the same procedure as used for Example26. The coupling employed DIC and HOBT. [N-Fmoc-hydroxylamine2-chlorotrityl resin was purchased from Novabiochem cat.# 01-64-0165.]

Preparation ofN-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-[4-(6-morpholin-4-yl-pyridin-3-yl)-buta-1,3-diynyl]-benzamide(5)

A solution of morpholine (300 uL) in NMP (1 ml) was added to a vialcontaining the 2-cloropyridine resin (4) (150 mg, 0.12 mmol). Thereaction mixture was purged with argon and heated to 85-90° C. for 24hours. The resin was drained and washed with DMF and DCM alternatelyseveral times. The product was cleaved from the resin through treatmentwith a TFA/water solution (80:20) (1.5 ml) for 45 min. The resin wasfiltered and washed with fresh TFA/water solution (80:20) (0.5 ml). Thecombined TFA and organic fractions were diluted with CH3CN/water (1:1)(10 ml), water (2 ml) and lyophilized. The crude product was purified byprep. HPLC. The crude product was dissolved in DMSO (1 ml), passedthrough a Teflon syringe filter; and the clear filtrate was injected ona preparative HPLC. The purification used a 20×50 mm Ultro 120 C18column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16min. The purified fractions were lyophilized to dryness to give 2.2 mgof pure product as the TFA salt (˜32% yield).

Example 27 Synthesis of4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide(4)

Preparation of2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonyloxy-butyrichydroxamic acid trityl resin (3)

Reagent MW EQ g/ml mmol H-Thr(Boc)-NHO-Trt Resin (1) 1.0  5.8 g 4.471,3-diynyl benzoic acid (2) 261.3 1.4 1.64 g 6.25 HOST 135.1 1.4 0.85 g6.25 DIC 126.2 1.4 0.98 ml 6.25 DIBA 129.25 3.5  2.7 ml 15.6 DMF   50 ml

DIEA (2.7 ml, 15.6 mmol) was added to a stirred solution of4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (2) (1.64 g, 6.3mmol), HOBT (0.85 g, 6.3 mmol), DIC (0.98 ml, 6.3 mmol) in DMF (50 ml).After 2 min., the Thr hydroxylamine resin (5.8 g, 4.5 mmol) was added inone portion. [N-Fmoc-hydroxylamine 2-chlorotrityl resin was purchasedfrom Novabiochem cat.# 01-64-0165.) After 12 hours at rt, the reactionwas found complete by LCMS. The resin was drained and washed with DMFand DCM alternately 3 times each. The product on resin 3 was used as isin subsequent reactions without further treatment.

Preparation of4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide(4)

Reagent MW EQ g/ml mmol 1,3-diynyl benzoic Thr Resin (3) 1.0 120 mg 0.09TFA/water (80:20)   1.5 ml

The product (4) (120 mg, 0.09 mmol) was cleaved from the resin throughtreatment with a TFA/water solution (80:20) (1.5 ml) for 45 min. Theresin was filtered and washed with fresh TFA/water solution (80:20) (0.5ml). The combined TFA and organic fractions were diluted withCH3CN/water (1:1) (10 ml), water (2 ml) and lyophilized. The crudeproduct was purified by prep. HPLC. The crude product was dissolved inDMSO (1 ml), passed through a Teflon syringe filter, and the clearfiltrate was injected on a preparative HPLC. The purification used a20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient(AcCN/water, 0.1% TFA) for 16 min. The purified fractions werelyophilized to dryness to give 2.2 mg of pure product as the TFA salt.The product (4) was lyophilized again from CH₃CN/water with 10equivalents of HCl to remove most of the TFA to yield 2 mg of product asthe HCl salt (˜53% yeild).

Example 28 Synthesis of4-{4-[4-(2-Dimethylamino-acetylamino)-phenyl]-buta-1,3-diynyl}-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide(6) (Continued from Compound 3 of Example 27 Above)

Preparation of2-(4-{4-[4-(2-Bromo-acetylamino)phenyl]-buta-1,3-diynyl}-benzoylamino)-3-tert-butoxycarbonyloxy-butyricacid hydroxamate trityl resin (5)

Reagent MW EQ g/ml mmol Amino 1,3-diynyl benzoic Thr Trt 1.0  0.75 g0.578 Resin (3) Bromo-acetyl chloride 157.4 8.0 0.728 g 4.62 Lutidine107 10.0  1.07 ml 9.24 DMF    6 ml

A solution of bromo-acetyl chloride (0.75 g, 0.58 mmol) in DCM (2 ml)was added to a mixture of2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonyloxy-butyricacid hydroxamate Trt Resin (3) (0.75 g, 0.58 mmol), lutidine (1.1 ml,9.2 mmol) and DCM (4 ml) at it with shaking. After shaking for 1.5hours, the reaction was found complete by LCMS. The resin was drainedand washed with DCM (2×10 ml), DMF (3×10 ml) and DCM (3×10 ml) again.The resin was drained and dried in vacuo. The product on resin 5 wasused as is in subsequent reactions without further treatment.

Preparation of4-{4-[4-(2-Dimethylamino-acetylamino)-phenyl]-buta-1,3-diynyl}-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide(6)

Reagent MW EQ g/ml mmol Bromo acetic Thr Trt Resin (5) 1.0 125 mg 0.093Dirnethyl amine 45.08  0.2 ml excess NMP  1.2 ml

A solution of dimethyl amine (0.2 ml) in NMP (1.2 ml) was added to bromoacetic Thr Trt Resin (5) (125 mg, 0.09 mmol) at rt with shaking. Aftershaking for 12 hours, the reaction was found complete by LCMS. The resinwas drained and washed with DCM (2×10 ml), DMF (3×10 ml) and DCM (3×10ml) again. The product (6) was cleaved from the resin through treatmentwith a TFA/Water solution (80:20) (1.5 ml) for 45 min. The resin wasfiltered and washed with fresh TFA/water solution (80:20) (0.5 ml). Thecombined TFA and organic fractions were diluted with CH3CN/water (1:1)(10 m]), water (2 ml) and lyophilized. The crude product was purified byprep. HPLC. The crude product was dissolved in DMSO (1 ml), passedthrough a Teflon syringe filter, and the clear filtrate was injected ona preparative HPLC. The purification used a 20×50 mm Ultro 120 C18column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16min. The purified fractions were lyophilized to dryness to give 2 mg ofpure product as the TFA salt (˜37% yeild).

Example 29 Synthesis of4-{4-[4-(2-Amino-4-methyl-pentanoylamino)-phenyl]-buta-1,3-diynyl}-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide(7) (Continued from Compound 3 of Example 27 Above)

Reagent MW EQ g/ml mmol Amino 1,3-diynyl benzoic Thr Trt 1.0   125 mg0.093 Resin (3) Fmoc-L-leucine 353.42 4.0 0.135 g 0.384 HATU 380 4.00.146 g 0.384 DLEA 129.25 8.0   133 ul 0.768 DMF  1.5 ml

A solution of Fmoc-L-leucine (0.135 g, 0.38 mmol), HATU (0.146 g, 0.38mmol) in DMF (1.5 ml) was made. After 2 min. of shaking, the activatedacid was added to the amino 1,3-diynyl benzoic Thr Trt Resin (3) (125mg, 0.09 mmol) at rt with shaking. After shaking for 36 hours, thereaction was drained and washed with DCM (2×4 ml), DMF (3×4 ml) and DCM(3×4 ml) again. The resin was treated with 20% piperizine in DMF (4 ml)for 2 hours twice. The resin was drained and washed with DMF and DCMalternately several times. The product was cleaved from the resinthrough treatment with a TFA/water solution (80:20) (1.5 ml) for 45 min.The resin was filtered and washed with fresh TFA/water solution (80:20)(0.5 ml). The combined TFA and organic fractions were diluted withCH3CN/water (1:1) (10 ml), water (2 ml) and lyophilized. The crudeproduct was purified by prep. HPLC. The crude product was dissolved inDMSO (1 ml), passed through a Teflon syringe filter, and the clearfiltrate was injected on a preparative HPLC. The purification used a20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient(AcCN/water, 0.1% TFA) for 16 min. The purified fractions werelyophilized to dryness to give 1.7 mg of pure product (7) as the TFAsalt (˜30% yield).

Examples 30-1307 of Table 1 were synthesized according to the syntheticschemes described above.

Biological Protocols and Data

P. aeruginosa LpxC Inhibition Assay

The assay followed the general method of Hyland et al (Journal ofBacteriology 1997 179, 2029-2037: Cloning, expression and purificationof UDP-3-O-acyl-GlcNAc deacetylase from Pseudomonas aeruginosa: ametalloamidase of the lipid A biosynthesis pathway) and theradiolabeling procedure is according to Kline et al. supra. Briefly,samples were incubated with 2 nM P. aeruginosa LpxC and 150 nM[3H-Ac]-UDP-3-OR-3-hydroxydecanoyl)-GlcNAc in a total volume of 50 uLfor 90 min at room temperature. Reactions were carried out in 96-wellpolypropylene plates in 50 mM sodium phosphate buffer, pH 7.5,containing 1 mg/mL BSA. Reactions were stopped by the addition of 180 uLof a 3% suspension of activated charcoal powder in 100 mM sodiumacetate, pH 7.5. Supernatants were clarified by centrifugation. Aportion of the clarified supernatant, containing the enzymaticallyreleased [3H]-acetate, was transferred to opaque white 96-well platescontaining scintillation fluid. The radioactivity was measured in aPerkin-Elmer/Wallac Trilux Microbeta counter. Control reactions to which5 mM EDTA had been added were included with each run to determinenonspecific tritium release.

Bacterial Screens and Cultures

Bacterial isolates were cultivated from −70° C. frozen stocks by twoconsecutive overnight passages at 35° C. in ambient air on 5% blood agar(Remel, Lenexa, Kans.). Clinical isolates tested were from a collectioncomposed of isolates collected during clinical trials and recentclinical isolates obtained from various geographically diverse hospitalsin the US. Quality control and primary panel strains were from theAmerican Type Culture Collection (ATCC; Rockville, Md.), with theexception of P. aeruginosa PAO200, a strain with a deletion of themexABoprM genes that was received from Dr. H. Schweizer. This straindoes not express the principal multidrug efflux pump and ishypersusceptible to many antibacterials. Strain Z61 (ATCC 35151) is alsohypersusceptible to antibacterials. It is thought that thehypersusceptibility of this strain is the result of increasedpermeability of its outer membrane (Angus B L et al, AntimicrobialAgents and Chemotherapy 1982 21,299-309: Outer membrane permeability inPseudomonas aeruginosa: Comparison of a wild-type with anantibacterial-supersusceptible mutant).

Susceptibility Testing

Minimum Inhibitory Concentrations (MICs) were determined by the brothmicrodilution method in accordance with the National Committee forClinical Laboratory Standards (NCCLS) guidelines. In brief, organismsuspensions were are adjusted to a 0.5 McFarland standard to yield afinal inoculum between 3×10⁵ and 7×10⁵ colony-forming units (CFU)/mL.Drug dilutions and inocula were made in sterile, cation adjustedMueller-Hinton Broth (Remel). An inoculum volume of 100 μl was added towells containing 100 μl of broth with 2-fold serial dilutions of drug.All inoculated microdilution trays were incubated in ambient air at 35°C. for 18-24 hours. Following incubation, the lowest concentration ofthe drug that prevented visible growth was recorded as the MIC.Performance of the assay was monitored by the use of laboratoryquality-control strains against tobramycin, that has a defined MICspectrum, in accordance with NCCLS guidelines.

Efficacy in Mouse Model of Systemic Pseudomonas aeruginosa Infection

Female Balb/c mice were injected intraperitoneally with 0.5 ml of abacterial suspension containing approximately 100 times the dose thatwould kill 50% of animals (LD₅₀) of P. aeruginosa strain PAO1 or E. coliATCC 25922. At one and five hours post infection, the test compound wasinjected intravenously in doses ranging from 5 mg/kg to 100 mg/kg, fivemice per group. Mice were observed for 5 days, and the dose of compoundresulting in survival of 50% of mice (ED₅₀) was calculated.

Drug Combination (Synergy) Studies

I. Principle

Checkerboard experiments can be performed to assess potentialinteractions between primary drug of interest (#1) and other relatedantibacterials (#2). P. aeruginosa ATCC 27853, S. aureus ATCC 29213 andother organisms can be used as challenge strains as well as selectedclinical isolates. Broth microdilution format can be used to assess theactivity of drug #1 and test compound alone and in combination. Twofolddilutions of the two compounds to be tested (each bracketing theexpected MIC value) are used. The fractional inhibitory concentration(FIC) was calculated as the MIC of compound #1 in combination with asecond compound, divided by the MIC of compound #1 alone. A summationFIC (ΣFIC) was computed for each drug combination as the sum of theindividual FICs of compound #1 and #2. Synergy was defined as anΣFIC≦0.5, indifference as an ΣFIC between 0.5 and 4, and antagonism asΣFIC>4. The lowest ΣFIC was used for the final interpretation of drugcombination studies.

Interpretation of Summation (ΣFIC)

a) Synergism, x≦0.5

b) Indifference, 0.5<x≦4

c) Antagonism, x>4 TABLE 2 Demonstration of Antibacterial activity ofSelect Compounds from Table 1 Enzyme inhibitory activity CompoundExample # IC₅₀ (nM) 12 <100 nM 572 <100 nM 481 <100 nM 19 <100 nM 516<100 nM 280 <100 nM 366 <100 nM 777 <100 nM 315 <100 nM 779 <100 nM 860<100 nM 801 <100 nM 13 <100 nM

TABLE 3 Antibacterial activity vs standard panel of organisms (MIC,μg/ml). MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C Bacterialstrain: hyper- P. P. S. permeable aeruginosa Compound aeruginosa E. coliaureus P. aerug. PAO200 Example # 27853 25922 29213 35151 mexAB 12 A A CA A 572 A A C A A 481 A A C A A 19 A A B A A 516 A A C A A 280 A A C A A366 A A C A A 777 A A C A A 315 A A C A A 779 A A C A A 860 A A C A A801 A A C A A 13 A A C AA A

TABLE 4 Antibacterial activity vs cystic fibrosis isolates ofPseudomonas aeruginosa (MIC, μg/ml). Strains have the followingphenotypes: 3198 and 3236, sensitive to most antibacterials; 2196,resistant to ciprofloxacin; 3224, resistant to ceftazidime; 3317,resistant to aztreonam; 1145 and 3206, multi-drug resistant. MIC KeyMIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50ug/ml = B MIC's of greater than 50 ug/ml = C Strain number: 3198 32362196 3224 3232 3317 1145 3206 Phenotype: Sensitive Sensitive Cipro RTobra R Ceftaz. R Aztr. R MDR MDR LpxC inhibitors  12 A A B A A A A A481 A A A A A A A A  19 A A A A A A A A 516 A A A A A A A A 280 A A B AA A A A 366 A A A A A A A A 777 A A A A A A A A 315 A A A A A A A A 779A A A A A A A A 801 A A A A A A A A  13 A A A A A A A A Comparatorantibacterials Tobramycin 2 0.5 2 64 1 2 8-32 64 Aztreonam 1 0.5 1 1 164 >128 >128 Ceftazidime 2 0.25 2 2 64 4 >128 >128 Cefepime 4 2 2 8 28 >128 32 Ciprofloxacin 1 0.06 >8 2 2 0.5 4 >8

TABLE 5 Antibacterial activity vs non-CF clinical isolates of P.aeruginosa and vs other gram- negative pathogens. Set 1: non-fermentingorganisms. P. aer., P. aeruginosa; Acinet. calc., Acinetobactercalcoaceticus; Alcal. xyl., Alcaligenes xylosoxidans; B. cep.,Burkholderia cepacia; S. malt., Stenotrophomonas maltophilia MIC KeyMIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50ug/ml = B MIC's of greater than 50 ug/ml = C Species: P. aer 27853 P.aer. PAO1 P. aer 12307 P. aer psa-6b Acinet. calc. Alcal. xyl B. cepaciaS. malt. LpxC inhibitors  12 A A A A A A B A 481 A A A A C C B C  19 A AA A A B B B 516 A A A C C C C 280 A A A A C B B B 366 A A A B C A B B777 A A B A B A C 315 A A A A C B A A 779 A A A C A A B 801 A A A B C BC  13 A A A C A A B Comparator antibacterials Tobramycin 8 2 2 64   64/>128 0.5 Aztreonam 16 32 32 32 64 >128/16    Ceftazidime 4 64 16 18/4 1 Cefepime 2 8 8 8 32/16 8/1 Meropenem 0.5 0.25 4 0.5 4 64 Pip/Tazo4 >128 8 1 64 16 Ciprofloxacin 0.5 2 0.5 0.5

TABLE 6 Antibacterial activity vs non-CF clinical isolates of P.aeruginosa and vs other gram- negative pathogens, continued. Set 2:enteric organisms. E. aer., Enterobacter aerogenes; E. clo.,Enterobacter cloacae; E. coli, Escherichia coli; K. pneu., Klebsiellapneumoniae; K. oxy., Klebsiella oxytoca; P. mir., Proteus mirabilis; S.marc., Serratia marcescens. MIC Key MIC's of 6.25 ug/ml or less = AMIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than50 ug/ml = C Species: E. aer. E. clo. E. coli 1619 E. coli 2788 K. pneu.K. oxy. P. mir. S. marc. LpxC inhibitors  12 C A A A A A A A 481 C A A AA A A A  19 A A A A A A A A 516 C B A B C C C A 280 C A A A B C B B 366C A A A B B A A 777 B A A A A A A A 315 C A A A C C C B 779 C A A A B BB A 801 B A A A A A A A  13 C A A A A A A A Comparator antibacterialsTobramycin 64 0.06 16/64 0.06/2   64 1 2 2 Aztreonam <=0.13 128/64 <=0.13/0.25     2 0.5 <=0.13 <=0.13 Ceftazidime 32 0.25 >128    0.25/<=0.13 8 0.25 <=0.13 0.25 Cefepime <=0.13       4/<=0.13 <=0.138 <=0.13 <=0.13 <=0.13 Meropenem 2 <=0.06 0.25/0.13 <=0.06 0.13 <=0.060.5 0.13 Pip/Tazo 2 >128 1 >128 2 0.25 1 Ciprofloxacin >8 0.015 2 0.030.06 0.03 0.03 0.25

TABLE 7 Drug Combination (Synergy) Studies Result Minimum Concentration(mg/ml) required to inhibit grouth of E. coli 25922 Erythromycin LpxCinhibitor 925 LpxC inhibitor 925 only — 6.25 Erythromycin only 128 —LpxC inhibitor 925 + erythromycin 2 0.78

Each of the Example compounds of Table 1 was synthesized and assayed asdescribed above. Many of the Example compounds 1-1307 displayed an IC₅₀value of less than 10 μM with respect to LpxC. Many of these compoundsdisplayed an IC₅₀ value of less than or equal to 1 μM or less than orequal to 0.1 μM. Many of these compounds exhibited IC₅₀ values of lessthan or equal to 0.050 μM, less than or equal to 0.030 μM, less than orequal to 0.025 μM, or less than or equal to 0.010 μM.

It should be understood that the organic compounds according to theinvention may exhibit the phenomenon of tautomerism. As the chemicalstructures within this specification can only represent one of thepossible tautomeric forms, it should be understood that the inventionencompasses any tautomeric form of the drawn structure. TABLE 1 ExampleStructure Name MH+ 30

3,4-difluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 275.2 31

(2S,3R)-N,3-dihydroxy-2-[(4- phenylbutanoyl)amino]butanamide 281.3 32

(2S,3R)-N,3-dihydroxy-2-({4-[4-(methyloxy)phenyl]butanoyl}amino)butanamide 311.3 33

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-5-phenyl-pentanamide 295.3 34

(2E,4E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl)-5-phenylpenta-2,4-dienamide 291.3 35

(2E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carboayl]propyl}-3-phenylprop-2-enaxnide 265.3 36

(2S,3R)-3-bydroxy-2-({(2E)-3-[4- (methyloxy)phenyl]prop-2-enoyl}amino)butanoic acid 280.3 37

(3R)-3-amino-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-phenylpentanamide 310.4 38

(2E)-3-(4-fluorophenyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}prop-2- enamide 283.3 39

(2E)-3-(3-bromophenyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}prop-2- enamide 344.2 40

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl)-4-{[(2-phenylethyl)amino]methyl}benzamide 372.4 41

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(4-phenylbutyl)amino]methyl)benzamide 400.5 42

4-[(cyclopropylamino)methyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 308.3 43

4-[(hexylamino)methyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 352.4 44

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-{[(2-pyridin-2-ylethyl)amino]methyl}benzamide 373.4 45

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-methylpiperazin-1-yl)benzamide 337.4 46

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(piperidin-1-ylmethyl)benzamide 336.4 47

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(morpholin-4-ylmethyl)benzamide 338.4 48

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({[3-(2-oxopyrrolidin-1- yl)propyl]amino}methyl)benzamide 393.5 49

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]prapyl}-4-{[(3-phenylpropyl)amino]methyl}benzamide 386.5 50

(2S,SR)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-phenylpyrrolidine-2-carboxamide 308.3 51

(2R,5S)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-phenylpyrrolidine-2-carboxamide 308.3 52

(2S,3R)-2-{[(3S)-3-amino-4-phenylbutanoyl]amino}-N,3-dihydroxybutanamide 296.3 53

(2S,3R)-2-{[(2S)-2-amino-4- phenylbutanoyl]amino}-N,3-dihydroxybutanamide 296.3 54

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6-(2-pyrrolidin-1-ylethyl)pyridine-3-carboxamide 337.4 55

2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxy-3-methylbutanoic acid 342.4 56

2-{[4-(4-ethylphenyl)phenyl]carbonylamino}- 3-hydroxy-4-methylpentanoicacid 356.4 57

{[(4-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}(thien-2-yl)acetic acid366.5 58

N-(2-{[(1,1-dimethylethyl)oxy]amino}-2-oxo-1-thien-2-ylethyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 437.6 59

3-(dimethylamino)-2-{[(4-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}propanoic acid 341.4 60

4′-ethyl-N-{(1S)-1-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)amino)carbonyl]-3-methylbutyl}-1,1′-biphenyl-4-carboxamide 456.6 61

4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-2-oxo-1-(phenylmethyl)ethyl]-1,1′-biphenyl-4- carboxamide 490.6 62

(2S)-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]- N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pyrrolidine- 2-carboxamide 440.5 63

4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]-1,1′- biphenyl-4-carboxamide 480.564

(3S)-2-[(4-ethyl-1,1′-biphenyl-4-yl)carbonyl]- N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 502.6 65

{(1S,2R)-2-hydroxy-1- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)-4- methylpentanamide 442.5 66

(2S,3R)-2-({(2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]-3-phenylpropanoyl}amino)- N,3-dihydroxybutanamide 476.567

(2S,3R)-2-{[(2S)-2-[(1,1′-biphenyl-4- ylacetyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino)-N,3- dihydroxybutanamide 492.5 68

(2S)-1-(1,1′-biphenyl-4-ylacetyl)-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pyrrolidine- 2-carboxamide 426.5 69

(2S,3R)-2-{[(2S)-2-[(1,1′-biphenyl-4- ylacetyl)amino]-3-(1H-imidazol-4-yl)propanoyl]amino}-N,3-dihydroxybutanamide 466.5 70

(2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]- N˜1˜-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pentanediamide 457.5 71

(3S)-3-[(1,1′-biphenyl-4-ylacetyl)amino]-4- ({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-4- oxobutanoic acid 444.5 72

(2S,4R)-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-4-hydroxy-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)pyrrolidine- 2-carboxamide 456.5 73

N-[(1S)-1-(aminomethyl)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-2-oxoethyl]-4′-ethyl-1,1′-biphenyl-4-carboxamide 429.5 74

4′-ethyl-N-{(1S)-1-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]but-3-ynyl)-1,1′-biphenyl-4-carboxamide438.5 75

(2S,3R)-2-({(2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]propanoyl}amino)-N,3- dihydroxybutanamide 400.4 76

(2S,4R)-1-(1,1-biphenyl-4-ylacetyl)-4- hydroxy-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pyrrolidine- 2-carboxamide 442.5 77

4′-ethyl-N-{(1R,2R)-2-hydroxy-1-[(hydroxy{[(2-hydroxyethyl)amino]carbonyl}amino)methyl]propyl}-1,1′-biphenyl-4-carboxamide416.5 78

N-((2R,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-3-hydroxybutyl)-N- hydroxymorpholine-4-carboxamide442.5 79

N-((2R,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-3-hydroxybutyl)-N-hydroxy-4-methylpiperazine-1-carboxamide 455.6 80

N-((1R,2R)-1-{[[(cyclopropylamino)carbonyl](hydroxy)amino]methyl}-2-hydroxypropyl)-4′-ethyl-1,1′-biphenyl-4-carboxamide 412.5 81

4′-ethyl-N-{(1R,2R)-2-hydroxy-1-[(hydroxy{[(pyridin-3-ylmethyl)amino]carbonyl}amino)methyl]propl}-1,1′-biphenyl-4-carboxamide 463.5 82

4′-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxy{[(2-pyridin-2-ylethyl)amino]carbonyl}amino)methyl]propyl}1,1′-biphenyl-4-carboxamide477.6 83

4′-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxy{[(4-morpholin-4-ylphenyl)amino]carbonyl}amino)methyl]propyl}-1,1′-biphenyl-4-carboxamide533.6 84

N˜1˜-((2R,3R)-2-{[(4′- yl)carbonyl]amino}-3-hydroxybutyl)-N˜1˜-hydroxypiperidine-1,4-dicarboxamide 483.6 85

4′-ethyl-N-[2-(hydroxyamino)ethyl]-1,1′- biphenyl-4-carboxamide 285.4 86

N-{2-[(aminocarbonyl)(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 328.4 87

N-{2-[(aminocarbonothioyl)(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 344.4 88

N-{2-[({[2-(dimethylamino)ethyl]amino}carbonyl)(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 399.5 89

N-{2-[{[(2-cyanoethyl)amino]carbonyl}(hydroxy)amino]ethyl}-4-ethyl-1,1′-biphenyl-4-carboxamide 381.4 90

4′-ethyl-N-(2-(hydroxy{[(2- hydroxyethyl)amino]carbonyl}amino)ethyl]-1,1′-biphenyl-4-carboxamide 372.4 91

N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxymorpholine-4-carboxamide 398.5 92

N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxy-4-methylpiperazine-1-carboxamide 411.5 93

N˜1˜-(2-{[(4-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N˜1˜-hydroxypiperidine-1,4-dicarboxamide 439.5 94

N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxypyrrolidine-1-carboxamide 382.5 95

N-{2-[[(cyclopropylamino)carbonyl](hydroxy)amino]ethyl}-4-ethyl-1,1′-biphenyl-4-carboxamide 368.4 96

4′-ethyl-N-{2-[hydroxy({[2- (methyloxy)ethyl]amino}carbonyl)amino]ethyl}-1,1′-biphenyl-4-carboxamide 386.5 97

N-{2-[({[2-(acetylamino)ethyl]amino}carbonyl)(hydroxy)amino]ethyl}-4′-ethyl-1,1-biphenyl-4-carboxamide 413.5 98

4′-ethyl-N-{2-[hydroxy({[3-(2-oxopyrrolidin-1-yl)propyl]amino}carbonyl)amino]ethyl}-1,1′- biphenyl-4-carboxamide 453.699

4′-ethyl-N-[2-(hydroxy{[(3- hydroxypropyl)amino]carbonyl}amino)ethyl]-1,1′-biphenyl-4-carboxamide 386.5 100

4′-ethyl-N-{2-[hydroxy({[3-(methyloxy)propyl]amino}carbanyl)amino]ethyl}-1,1′-biphenyl-4-carboxamide400.5 101

N-(2-{[(4′-ethyl-1,1-biphenyl-4- yl)carbonyl]amino)ethyl)-N-hydroxy-1,4′- bipiperidine-1′-carboxamide 479.6 102

4′-ethyl-N-[2-(hydroxy{[(2-pyridin-2-ylethyl)amino]carbonyl}amino)ethyl]-1,1′- biphenyl-4-carboxamide 433.5103

4′-ethyl-N-[2-(hydroxy{[(pyridin-3-ylmethyl)amino]carbonyl}amino)ethyl]-1,1′- biphenyl-4-carboxamide 419.5104

4′-ethyl-N-[2-(hydroxy{[(4-morpholin-4-ylphenyl)amino]carbonyl}amino)ethyl]-1,1 ′- biphenyl-4-carboxamide 489.6105

N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N,3-dihydroxypiperidine-1-carboxamide 412.5 106

N-{2-[{[(3-aminocyclohexyl)amino]carbonyl}(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 425.5 107

N-{2-[{[(2-aminoethyl)amino]carbonyl}(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 371.4 108

N-{2-[{[(3-aminopropyl)amino]carbonyl}(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 385.5 109

1,1-dimethylethyl 3-({[(2-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}ethyl)(hydroxy)amino]carbonyl}amino)propylcarbamate485.6 110

4′-ethyl-N-{2-[({[(4-fluorophenyl)methyl]amino}carbonyl)(hydroxy)amino]ethyl}-1,1′-biphenyl-4-carboxamide 436.5 111

N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxy-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxamide 493.5 112

N-{2-[{[(4-aminothien-3- yl)amino]caxbonyl}(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 425.5 113

4′-ethyl-N-(2-{hydroxy[(piperidin-3-ylamino)carbonyl]amino}ethyl)-1,1′-biphenyl- 4-carboxamide 411.5 114

4′-ethyl-N-(2-{hydroxy[(piperidin-4-ylamino)carbonyl]amino}ethyl)-1,1′-biphenyl- 4-carboxamide 411.5 115

4′-ethyl-N-[2-(hydroxy{[(piperidin-2-ylmethyl)amino]carbonyl}amino)ethyl]-1,1′- biphenyl-4-carboxamide 425.5116

4′-ethyl-N-[2-(hydroxy{[(piperidin-3-ylmethyl)amino]carbonyl}amino)ethyl]-1,1′- biphenyl-4-carboxamide 425.5117

3-amino-N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxypyrrolidine-1-carboxamide 397.5 118

1,1-dimethylethyl 3-[({[(2-{[(4-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}ethyl)(hydroxy)amino]carbonyl}amino)methyl]piperidine-1-carboxylate525.7 119

1,1-dimethylethyl 1-{[(2-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}ethyl)(hydroxy)amino]carbonyl}pyrrolidin-.3-ylcarbamate497.6 120

4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2-(hydroxyamino)ethyl]amino}carbonyl)propyl]- 1,1′-biphenyl-4-carboxamide386.5 121

N-{(1S,2R)-1-[({2-[(aminocarbonyl)(hydroxy)amino]ethyl}amino)carbonyl]-2-hydroxypropyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 429.5 122

N-{(1S,2R)-1-[({2-[(aminocarbonothioy)(hydroxy)amino]ethyl}amino)carbonyl]-2-hydroxypropyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 445.6 123

4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2-(hydxoxy{[(2-hydroxyethyl)amino]carbonyl}amino)ethyl]amino}carbonyl)propyl]-1,1′-biphenyl-4-carboxamide473.5 124

4′-ethyl-N-{(1S)-6-hydroxy-1-[(1R)-1-hydroxyethyl]-2,7-dioxo-11-oxa-3,6,8-triazadodec-1-yl}-1,1-biphenyl-4-carboxamide 487.6 125

4′-ethyl-N-{(1S)-6-hydroxy-1-[(1R)-1-hydroxyethyl]-11-methyl-2,7-dioxo-3,6,8,11-tetraazadodec-1-yl}-1,1′-biphenyl-4-carboxamide 500.6 126

4′-ethyl-N-{(1S)-6-hydroxy-1-[(1R)-1-hydroxyethyl]-2,7,12-trioxo-3,6,8,11-tetraazatridec-1-yl}-1,1′-biphenyl-4- carboxamide 514.6 127

4′-ethyl-N-{(1S,2R)-2-hydroxy-1-[(}2- [hydroxy({[3-(2-oxopyrrolidin-1-yl)propyl]amino}carbonyl)amino]ethyl}amino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 554.7 128

N-{(1S,2R)-1-[({2-[{[(2- cyanoethyl)amino]carbonyl}(hydroxy)amino]ethyl}amino)carbanyl]-2- hydroxypropyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 482.6 129

N-{(1S,2R)-1-[({2-[[(cyclopropylamino)carbonyl](hydroxy)amino]ethyl}amino)carbonyl]-2-hydroxypropyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 469.6 130

N-{2-[((2S,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxybutanoyl)amino]ethyl}-N- hydroxypyrrolidine-1-carboxamide 483.6131

N-{2-[((2S,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxybutanoyl)amino]ethyl}-N- hydroxymorpholine-4-carboxamide 499.6132

N-{2-[((2S,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxybutanoyl)amino]ethyl}-N- hydroxy-4-methylpiperazine-1-carboxamide 512.6 133

4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2- (hydroxy{[(pyridin-3-ylmethyl)amino]carbonyl}amino)ethyl]amino}carbonyl)propyl]-1,1′-biphenyl-4-carboxamide520.6 134

4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2- (hydroxy{[(2-pyridin-2-ylethyl)amino]carbonyl}amino)ethyl]amino}carbonyl)propyl]-1,1′-biphenyl-4-carboxamide534.6 135

3-chloro-N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(trifluoromethyl)oxy]benzamide 357.7 136

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(3-nitrophenyl)methyl]oxy)benzamide 390.4 137

(4R)-2-(4-fluoro-3-prop-2-enylphenyl)-N-hydroxy-4,5-dihydro-1,3-oxazole-4-carboxamide 265.3 138

3-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydxoxyamino)carbonyl]propyl}-4-(methyloxy)benzamide 287.3 139

4-(but-3-enyloxy)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 309.3 140

3-bromo-5-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-4-(prop-2- enyloxy)benzamide 392.2 141

4-fluoro-N-{(1S,2S)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)-3-prop-2- enylbenzamide 297.3 142

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(prop-2-enyloxy)-3-(trifluoromethyl)benzamide 363.3 143

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(methyloxy)benzamide 269.3 144

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-(phenyloxy)benzamide 331.3 145

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-(methyloxy)-3-[(trifluoromethyl)oxy]benzamide 353.3 146

N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(trifluoromethyl)oxy]benzamide 323.2 147

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(trifluoramethyl)oxy]benzamide 323.2 148

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(trifluoromethyl)benzamide 307.2 149

3,4-difluoro-N-{(2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 275.2 150

N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(methyloxy)benzamide 269.3 151

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-propyl-1,1′-biphenyl-4-carboxamide 357.4 152

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-propyl-1,1′-biphenyl-4-carboxamide 357.4 153

N-{(1S,2R)-2-hydxoxy-1- [(hydroxyamino)carbonyl]propyl}-4-[trifluoro(methylidene)-lambda˜6˜- sulfanyl]benzamide 341.3 154

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 239.2155

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 315.3 156

3-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(methyloxy)benzamide 348.2 157

4-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-(prop-2-enyloxy)benzamide 313.3 158

2,3,5,6-tetrafluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-4-prop-2- enylbenzamide 351.3 159

3-fluoro-N-{(1S,2R)-2-hydroxy-1- {(hydroxyamino)carbonyl]propyl}-5-(trifluoromethyl)benzamide 325.2 160

4-bromo-2-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 336.1 161

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(phenyloxy)benzamide 331.3 162

4-(dimethylamino)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)caxbonyl]propyl}benzamide 282.3 163

2-[3-fluoro-4-(methyloxy)-5-prop-2-enylphenyl]-N-hydroxy-4,5-dihydro-1,3- oxazole-4-carboxamide 295.3 164

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-{3-(trifluoromethyl)phenyl]furan-2-carboxamide 373.3 165

4-{[(1E)-1,2-difluorobuta-1,3-dienyl]oxy}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 343.3 166

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}quinoline-2-carboxamide 290.3 167

N-[2-(hydroxyamino)-1-(hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl-4-carboxamide 301.3 168

N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 315.3 169

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2′-methyl-1,1′-biphenyl-4-carboxamide 329.4 170

N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(trifluoromethyl)benzamide 307.2 171

4-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-(trifluoromethyl)benzamide 325.2 172

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(3-nitrophenyl)oxy]methyl}benzamide 390.4 173

N-[(1R)-2-(hydroxyamino)-1- (mercaptomethyl)-2-oxoethyl]-4-[(trifluoromethyl)oxy]benzamide 325.3 174

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,3-benzodioxole-5-carboxamide 283.3 175

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6-(trifluoromethyl)pyridine-3-carboxamide 308.2 176

N-{3-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(trifluoromethyl)oxy]benzamide 323.2 177

N-{3-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 315.3 178

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[hydroxy(phenyl)methyl]benzamide 345.4 179

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[({4-[(trifluoromethyl)oxy]phenyl}oxy)methyl]benzamide 429.4 180

4-[({4-bromo-2- [(trifluoromethyl)oxy]phenyl}oxy)methyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide508.3 181

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-3-nitro-1,1′-biphenyl-4-carboxamide 360.3 182

4-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide318.1 183

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-(methyloxy)-1,1′-biphenyl-4-carboxamide 345.4 184

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-[(trifluoromethyl)oxy]-1,1′-biphenyl-4- carboxamide 399.3 185

4′-(ethyloxy)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)-1,1′- biphenyl-4-carboxamide 359.4 186

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{5-[(Z)-(hydroxyimino)methyl]thien-2-yl}benzamide 364.4 187

3′-(ethyloxy)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 359.4 188

(2R,3R)-N,3-dihydroxy-1-( {4- [(trifluoromethyl)oxy]phenyl}carbonyl)pyrrolidine-2-carboxamide 335.2 189

N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- oxoethyl]-3-(1-methylethyl)-4-(methyloxy)benzamide 297.3 190

N-[2-(hydroxyamino)-1-(hydroxymethyl)-2-oxoethyl]-3-(1-methylethyl)-4-(prop-2- enyloxy)benzamide 323.4 191

N-[2-(hydroxyamino)-1-(hydroxymethyl)-2-oxoethyl]-4-(methyloxy)-3-propylbenzamide 297.3 192

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(methylthio)-1,1′-biphenyl-4-carboxamide 361.4 193

5-bromo-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}thiophene-2- carboxamide 324.2 194

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-{4-[(trifluoromethyl)oxy]phenyl}thiophene-2- carboxamide 405.4 195

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1-benzofuran-2-carboxamide 279.3 196

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-phenylthiophene-2-carboxamide 321.4 197

4′-(dimethylamino)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 358.4 198

(2S,3R)-N,3-dihydroxy-2-[({2-[(trifluoromethyl)oxy]phenyl}acetyl)amino]butanamide 337.3 199

5-[4-(ethyloxy)phenyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}thiophene- 2-carboxamide 365.4 200

5-[3-(ethyloxy)phenyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}thiophene- 2-carboxamide 365.4 201

(4R)-N-hydroxy-2-{2′-[(trifluoromethyl)oxy]-1,1′-biphenyl-4-yl)-4,5-dihydro-1,3-oxazole-4- carboxamide 367.3 202

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-(hydroxymethyl)-1,1′-biphenyl-4-carboxamide 345.4 203

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl]-4-{5-[(4-methylpiperazin-1-yl)methyl]thien-2-yl}benzamide 433.5 204

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(methyloxy)phenyl]carbonyl}benzamide 373.4 205

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(E)-phenyldiazenyl]benzamide 343.4 206

(4R)-N-hydroxy-2-{4-(methyloxy)-3-[(trifluoromethyl)oxy]phenyl)-4,5-dihydro-1,3- oxazole-4-carboxamide321.2 207

4′-ethyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 343.4 208

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4′-(trifluoromethyl)-1,1′-biphenyl-4-carboxamide 383.3 209

5-(4-ethylphenyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}thiophene-2- carboxamide 349.4 210

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-[4-(methyloxy)phenyl]thiophene-2-carboxamide 351.4 211

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-[4-(methylthio)phenyl]thiophene-2-carboxamide 367.5 212

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-(3-nitrophenyl)thiophene-2-carboxamide 366.4 213

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-axo-4H-chromene-2-carboxamide 307.3 214

N-[1-[(hydroxyamino)carbonyl]-1- (hydroxymethyl)-2-methylpropyl]-4-[(trifluoromethyl)oxy]benzamide 351.3 215

N-[2-hydroxy-3-(hydroxyamino)-3-oxopropyl]- 1,1′-biphenyl-4-carboxamide301.3 216

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4-[(E)-2-phenylethenyl]benzamide 341.4 217

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-9H-fluorene-2-carbaxamide 327.4 218

4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]-1,1-biphenyl-4-carboxylic acid 359.3 219

N-[2-(hydroxyamino)-1-(hydroxymethyl)-2-oxoethyl]-4-(prop-2-enyloxy)-3-propylbenzamide 323.4 220

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4- iodobenzamide365.1 221

4′-hydroxy-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 331.3 222

6-bromo-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pyridine-2- carboxamide 319.1 223

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6-phenylpyridine-2-carboxamide 316.3 224

4′-butyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 371.4 225

4′-(1,1-dimethylethyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 371.4 226

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-[3-(methyloxy)phenyl]thiophene-2-carboxamide 351.4 227

4′-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]-1,1′-biphenyl-4-yl dihydrogen phosphate 411.3 228

N-ethyl-N′-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4,4′-dicarboxamide 386.4 229

N-[(1S,2R)-1-(hydrazinocarbonyl)-2-hydroxypropyl]-4′-propyl-1,1′-biphenyl-4- carboxamide 356.4 230

N-{(1S,2R)-2-hydroxy-1- [(methylamino)carbanyl]propyl}-4′-propyl-1,1′-biphenyl-4-carboxamide 355.4 231

N-[(1S,2R)-1-(hydrazinocarbonyl)-2-hydroxypropyl]-4-(methyloxy)benzamide 268.3 232

(2S,3R)-2-[(1,1′-biphenyl-4-ylsulfonyl)amino]- N,3-dihydroxybutanamide351.4 233

4-hydroxy-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 255.2 234

3′-cyano-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-1,1′-biphenyl-4-carboxamide 340.3 235

1,1-dimethylethyl ({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}oxy)acetate 369.4236

(2S,3R)-2-[(1,1′-biphenyl-4- ylsulfonyl)(methyl)amino]-N,3-dihydroxybutanaimde 365.4 237

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3′-[(Z)-(hydroxyimino)methyl]-4′-(methyloxy)-1,1′- biphenyl-4-carboxamide 388.4238

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(phenylcarbonyl)amino]benzamide 358.4 239

N-hydroxy-2-[3-(1-methylethyl)-4-(prop-2-enyloxy)phenyl]-4,5-dihydro-1,3-oxazole-4- carboxamide 305.3 240

4′-butyl-N-{(1S,2R)-2-hydroxy-1-[(methylamino)carbonyl]propyl}-1,1′-biphenyl- 4-carboxamide 369.5 241

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(5-methylpyridin-2-yl)benzamide 330.4 242

5-bromo-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pyridine-3- carboxamide 319.1 243

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-pyridin-3-ylbenzamide 316.3 244

N-{(1R,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-N′-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4,4-dicarboxamide 475.5 245

(2S,3R)-N,3-dihydroxy-2-[({4-[(E)-2-phenylethenyl]phenyl)methyl)amino]butanamide 327.4 246

4-{[(4-bromophenyl)sulfonyl]amino)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 473.3 247

1,1-dimethylethyl 4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}amino)-4-oxobutylcarbamate439.5 248

4-[(4-aminobutanoyl)amino]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 339.4 249

1,1-dimethylethyl{4′-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)methyl]-1,1′-biphenyl-4-yl}methylcarbamate 430.5 250

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-pyrimidin-5-ylbenzamide 317.3 251

1,1-dimethylethyl 5-{4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl)pyridine-3-carboxylate 416.4 252

5-{4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}pyridine-3-carboxylic acid 360.3 253

(4S)-N-hydroxy-2-{4-(methyloxy)-3-[(trifluoromethyl)oxy]phenyl}-4,5-dihydro-1,3- oxazole-4-carboxamide321.2 254

(2S,3R)-2-({[4′-(aminomethyl)-1,1′-biphenyl-4-yl]methyl)amino)-N,3-dihydroxybutanamide 330.4 255

(3S)-1-hydroxy-3-[(1R)-1-hydroxyethyl]-4-({4-[(E)-2-phenylethenyl]phenyl}methyl)piperazine-2,6-dione 367.4 256

(2S,3R)-N,3-dihydroxy-2-({[4- (phenylethynyl)phenyl]methyl}amino)butanamide 325.4 257

N-(3-aminopropyl)-N′-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzene-1,4- dicarboxamide 339.4 258

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(propanoylamino)benzamide 310.3 259

1,1-dimethylethyl 3-[({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}carbonyl)amino]propylcarbamate 439.5 260

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-(phenyloxy)-1,1′-biphenyl-4-carboxamide 407.4 261

N-[(1S,2R)-1-({[cyano(phenyl) methyl]amino}carbonyl)-2-hydroxypropyl]-4′-hydroxy-1,1′-biphenyl-4- carboxamide 430.5 262

4′-{[2-(hydroxyamino)-2-oxoethyl]oxy}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)-1,1′- biphenyl-4-carboxamide 404.4 263

4-({[(1S,2R)-1- {[(cyanomethyl)amino]carbonyl}-2-(propanoyloxy)propyl]amino}carbonyl)-1,1′- biphenyl-4-yl propanoate466.5 264

4′-({[(1S,2R)-1- {[(cyanomethyl)(propanoyl)amino]carbonyl}-2-(propanoyloxy)propyl]amino}carbonyl)-1,1′- biphenyl-4-yl propanoate522.6 265

N-((1S,2R)-1-{[(cyanomethyl)amino]carbonyl}-2-hydroxypropyl)-4′-hydroxy-1,1′-biphenyl-4- carboxamide 354.4 266

(2S,3S)-2-[(1,1′-biphenyl-4-ylmethyl)amino]- N,3-dihydroxybutanamide301.4 267

N-{2-hydroxy-1-[(hydroxyamino)carbonyl]-2-phenylethyl}-1,1′-biphenyl-4-carboxamide 377.4 268

(2S,3R)-2-[(diphenylacetyl)amino]-N,3- dihydroxybutanamide 329.4 269

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6-[(phenylmethyl)thio]pyridine-3-carboxamide 362.4 270

N,3-dihydroxy-2-({[4- (phenyloxy)phenyl]methyl}amino)butanamide 317.4271

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2′-[(trifluoromethyl)oxy]-1,1′-biphenyl-4- carboxamide 399.3 272

(2R,3S)-2-[(1,1′-biphenyl-4-ylmethyl)amino]- N,3-dihydroxybutanamide301.4 273

4-{({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]benzoic acid 283.3 274

1,1-dimethylethyl 4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl]amino) carbonyl]benzoate 339.4 275

(4R)-4-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-5-(hydroxyamino)-5- oxopentanoic acid 371.4 276

4′-ethyl-N-[(1R)-2-(hydroxyamino)-1-(hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl- 4-carboxamide 329.4 277

4′-ethyl-N-[(1S)-2-(hydroxyamino)-1-(hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 329.4 278

(2S)-1-[(4′-ethyl-1,1-biphenyl-4-yl)carbonyl]-N,4-dihydroxypyrrolidine-2-carboxamide 355.4 279

4′-ethyl-N-{(1S)-1- [(hydroxyamino)carbonyl]but-3-ynyl}-1,1′-biphenyl-4-carboxamide 337.4 280

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1-biphenyl-4-carboxamide 328.4 281

N-{(1S)-1-[(hydroxyamino)carbonyl]-2-methylpropyl)-1,1′-biphenyl-4-carboxamide 313.4 282

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-N-methyl-1,1′-biphenyl-4-carboxamide 329.4 283

4-ethynyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 263.3 284

4-(1,3-benzodioxol-5-yl)-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 359.3 285

N-{(1R,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-propyl-1,1′-biphenyl-4-carboxamide 357.4 286

2-({[3′-(ethyloxy)-1,1′-biphenyl-4-yl]methyl}amino)-N,3-dihydroxybutanamide 345.4 287

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3′,4′-bis(methyloxy)-1,1′-biphenyl-4-carboxamide 375.4 288

3′-formyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-(methyloxy)-1,1′-biphenyl-4-carboxamide 373.4 289

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}buta-1,3-diynyl)benzamide 523.5 290

(2S,3R)-2-({[4-(ethyloxy)-1,1′-biphenyl-4-yl]methyl}amino)-N,3-dihydroxybutanamide 345.4 291

3′-chloro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-(methyloxy)-1,1′-biphenyl-4-carboxamide 379.8 292

(1R,2R)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2-phenylcyclopropanecarboxamide 279.3 293

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-(1H-pyrrol-1-yl)benzamide 304.3 294

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-propylbenzamide 281.3 295

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-pentylbenzamide 309.4 296

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-octylbenzamide 351.5 297

(2E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-(4-methylphenyl)prop-2-enamide 279.3 298

(2E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-[4-(trifluoromethyl)phenyl]prop-2-enamide 333.3 299

(2E)-3-(1,1′-biphenyl-4-yl)-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}prop-2-enamide 341.4 300

(2S,3R)-2-[(1,1-biphenyl-4-ylacetyl)amino]- N,3-dihydroxybutanamide329.4 301

(2S,3R)-2-{[(2S)-2-amino-3-(1,1′-biphenyl-4-yl)propanoyl]amino}-N,3-dihydroxybutanamide 358.4 302

(2S,3R)-2-{[(2R)-2-amino-3-(1,1′-biphenyl-4-yl)propanoyl]amino}-N,3-dihydroxybutanamide 358.4 303

(3S)-3-amino-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-5-phenylpentanamide 310.4 304

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(phenylamino)methyl]benzamide 344.4 305

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-}[(phenylmethyl)amino]methyl}benzamide 358.4 306

4′-ethyl-N-{(1S,2R)-2-hydroxy-1-[({(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 444.5 307

(2S,3R)-2-[(1,1′-biphenyl-4-ylacetyl)amino]-3-hydroxy-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}butanamide 430.5 308

4-(4-chlorophenyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}cyclohexane carboxamide 355.8 309

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1H-pyrazol-1-yl)benzamide 305.3 310

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-morpholin-4-ylbenzamide 324.3 311

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1,2,3-thiadiazol-4-yl)benzamide 323.3 312

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-methylpiperazin-1-yl)methyl]benzamide 351.4 313

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1H-imidazol-1-ylmethyl)benzamide 319.3 314

(2S,4S)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-phenylpyrrolidine-2-carboxamide 308.3 315

4′-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 394.2 316

4′-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 394.2 317

4′-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 394.2 318

(2R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-N˜1˜-hydroxypentanediamide 370.4 319

(2S,3S)-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-3-hydroxypyrrolidine-2- carboxylic acid 340.4 320

(2S,3S)-N-[(1,1-dimethylethyl)oxy]-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-3- hydroxypyrrolidine-2-carboxamide411.5 321

(2S,3S)-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-N,3-dihydroxypyrrolidine-2- carboxamide 355.4 322

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-nitrophenyl)ethynyl]benzamide 384.4 323

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(1H-pyrrol-1-yl)phenyl]ethynyl}benzamide 404.4 324

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-nitro-1,1′-biphenyl-4-carboxamide 360.3 325

(2S,3R)-N,3-dihydroxy-2-({[4-(methyloxy)-3′- propyl-1,1′-biphenyl-4-yl]methyl}amino)butanamide 373.5 326

4′-cyano-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′-biphenyl-4-carboxamide 340.3 327

(2S,3R)-2-({[4′-(ethyloxy)-4-(methyloxy)-1,1′-biphenyl-3-yl]methyl}amino)-N,3- dihydroxybutanamide 375.4 328

2′,5′-difluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 351.3 329

N-[(1S)-1-[(acetylamino)methyl]-2-(hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 370.4330

N-{(1S)-4-amino-1- [(hydroxyamino)carbonyl]butyl}-4-ethyl-1,1′-biphenyl-4-carboxamide 356.4 331

4′-ethyl-N-[(1S)-2-(hydroxyamino)-1-(1H-imidazol-5-ylmethyl)-2-oxoethyl]-1,1′- biphenyl-4-carboxamide 379.4 332

(2S,3R)-2-{[1-(1,1′-biphenyl-4- yl)ethyl]amino}-N,3-dihydroxybutanamide329.4 333

(2S,3R)-2-{[1-(1,1′-biphenyl-4- yl)propyl)amino}-N,3-dihydroxybutanamide329.4 334

(2S,3R)-2-{[1-(4′-bromo-1,1′-biphenyl-4-yl)ethyl]amino}-N,3-dihydroxybutanamide 394.3 335

(2S,3R)-N,3-dihydroxy-2-{[1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]amino}butanamide 329.4 336

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-1,1′-biphenyl-4-carboxamide 300.3 337

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(1H-pyrrol-1-yl)benzamide 289.3 338

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-chlorophenyl)cyclohexanecarboxamide 340.8 339

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-pentylbenzamide294.4 340

(2E)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-3-(1,1′-biphenyl- 4-yl)prop-2-enamide 326.4341

(2S)-3-amino-2-{[(4′-ethyl-1,1′-biphenyl-4-yl)methyl]amino}-N-hydroxypropanamide 314.4 342

(2S)-3-amino-2-[(1,1′-biphenyl-4- ylmethyl)amino]-N-hydroxypropanamide286.3 343

(2S)-3-amino-2-{[1-(4′-bromo-1,1′-biphenyl-4-yl)ethyl]amino}-N-hydroxypropanamide 379.3 344

(2S)-3-amino-N-hydroxy-2-{[1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]amino}propanamide 314.4 345

4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-1-(hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 430.5 346

4′-ethyl-N-{(1S)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)amino)-1-[(4-hydroxyphenyl)methyl]-2-oxoethyl}-1,1′- biphenyl-4-carboxamide 506.6 347

(2S)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-N˜1˜-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pentanediamide 471.5 348

(4S)-4-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-5-({(1S,2R)-2-hydroxy-1-[(hydroxyaxmno)carbonyl]propyl}amino)-5- oxopentanoic acid 472.5 349

(3S)-3-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino)-4-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-4- oxobutanoic acid 458.5 350

(3S)-2-(1,1′-biphenyl-4-ylacetyl)-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 488.6 351

4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-1-methyl-2-oxoethyl]-1,1-biphenyl-4-carboxamide 414.5 352

(2S,3R)-2-({(2S)-3-amino-2-[(1,1′-biphenyl-4-ylacetyl)amino]propanoyl}amino)-N,3- dihydroxybutanamide 415.5 353

(2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)pent-4- ynamide 424.5 354

(25,3R)-2-{[(2S)-2-amino-2-(1,1′-biphenyl-4-yl)ethanoyl]amino}-N,3-dihydroxybutanamide 344.4 355

(2S,3R)-2-{[(2R)-2-amino-2-(1,1′-biphenyl-4-yl)ethanoyl]amino}-N,3-dihydroxybutanamide 344.4 356

N-(3-aminopropyl)-4′-ethyl-N-[2-(hydroxyamino)-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 356.4 357

N-(2-cyanoethyl)-4′-ethyl-N-[2-(hydroxyamino)-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 352.4 358

N-{2-(acetylamino)ethyl]-4′-ethyl-N-[2-(hydroxyamino)-2-oxoethyl]-1,1-biphenyl-4- carboxamide 384.4 359

4′-ethyl-N-[2-(hydroxyamino)-2-oxoethyl]-N-prop-2-ynyl-1,1′-biphenyl-4-carboxamide 337.4 360

4-cyano-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide264.3 361

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-cyanobenzamide249.2 362

1,1-dimethylethyl (2S)-2-{[(4- ethynylphenyl)carbonyl}amino]-3-(hydroxyamino)-3-oxopropylcarbamate 348.4 363

1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-[({4-[(E)-2-phenylethenyl]phenyl}methyl)amino]propylcarbamate 412.5 364

N-{(1R,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-3′-(trifluoromethyl)-1,1′-biphenyl-4-carboxamide 383.3 365

(2S,3R)-2-[(1,1′-biphenyl-4-ylmethyl)amino]-3- hydroxybutanoic acid286.3 366

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(phenylethynyl)benzamide 324.4 367

1,1-dimethylethyl (2S)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl carbamate 424.5368

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-ethynylbenzamide248.3 369

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-ethynylbenzamide248.3 370

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(methyloxy)phenyl]ethynyl}benzamide 369.4 371

(2S)-3-amino-N-hydroxy-2-[({4-{(E)-2-phenylethenyl]phenyl}methyl)amino]propanamide 312.4 372

1,1-dimethylethyl 2-{4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbanyl]-1,1′-biphenyl-4-yl}ethylcarbamate 458.5 373

(2S,3R)-N,3-dihydroxy-2-[({4′-[(2-pyrrolidin-1-ylethyl)oxy]-1,1-biphenyl-4- yl}methyl)amino]butanamide 414.5 374

1,1-dimethylethyl (1S)-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-({[4- ({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]amino}carbanyl)butylcarbamate 668.8 375

4-(4-chlorophenyl)-N-[(1S)-2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-1-methyl-2-oxoethyl]cyclohexanecarboxamide 426.9 376

4′-ethyl-N-[2-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-2-oxoethyl]-1,1′-biphenyl-4-carboxamide 400.4 377

4′-ethyl-N-[3-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-3-oxopropyl]-1,1′-biphenyl-4-carboxamide 414.5 378

4′-ethyl-N-[4-({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-4-oxobutyl]-1,1′-biphenyl-4-carboxamide 428.5 379

N-((1S)-2-([(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]amino}-1-methyl-2-oxoethyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 399.5 380

N-(2-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-2-oxoethyl)-4-ethyl-1,1′-biphenyl-4- carboxamide 385.4 381

N-(3-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-3-oxopropyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 399.5 382

N-(4-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-4-oxobutyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 413.5 383

4′-ethyl-N-[1-[(hydroxyamino)carbonyl]-2-(methyloxy)propyl]-1,1′-biphenyl-4- carboxamide 357.4 384

4′-ethyl-N-[(1S,2R)-1- [(hydroxyamino)carbonyl]-2-(methyloxy)propyl]-1,1′-biphenyl-4- carboxamide 357.4 385

N-[1-[(dimethylamino)methyl]-2-(hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 356.4386

N-{(1S)-3-cyano-1- [(hydroxyamino)carbonyl]propyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 352.4 387

N-{(1S)-5-amino-1- [(hydroxyamino)carbonyl]pentyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 370.5 388

N-{(1S)-3-amino-1- [(hydroxyamino)carbonyl]propyl}-4′-ethyl-1,1′-biphenyl-4-carboxamide 342.4 389

4′-ethyl-N-hydroxy-1,1′-biphenyl-4-carboxamide 242.3 390

4′-ethyl-N-{2-hydroxy-1- [(hydroxyamino)carbonyl]-2-methylpropyl}-1,1′-biphenyl-4-carboxamide 357.4 391

N-[(2S)-2-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-3-(hydroxyamino)-3-oxopropyl]morpholine-4-carboxamide 441.5 392

N-[(1S)-1-{[(aminocarbonyl)amino]methyl}-2-(hydroxyamino)-2-oxoethyl]-4-ethyl-1,1′- biphenyl-4-carboxamide 371.4393

N-[(1S)-1-({[amino(imino)methyl]amino}methyl)-2-(hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 370.4394

N-[(2S)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4′-ethyl-1,1′-biphenyl-4-carboxamide 328.4 395

1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-N-hydroxypiperazine-2-carboxamide 354.4 396

N-[(2S)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4{phenylethynyl)benzamide324.4 397

N-hydxoxy-1-{[4- (phenylethynyl)phenyl]carbonyl}piperazine-2-carboxamide 350.4 398

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-pentylphenyl)ethynyl]benzamide 409.5 399

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[3-(methyloxy)phenyl]ethynyl}benzamide 369.4 400

4-[(3-fluoro-4-methylphenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 371.4 401

4-[(2,4-difluorophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 375.3 402

methyl (2E)-3-(ethylamino)-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)but-2-enoate 363.4 403

1,1-dimethylethyl 4-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-4-oxobutylcarbamate509.6 404

N-(1-(N-hydroxycarbamoyl)-2-hydroxy-3- methylbutyl)[4-(4-ethylphenyl)phenyl]carboxamide 371.4 405

N-((1R,2R)-1-{[(aminocarbonyl)(hydroxy) amino]methyl}-2-hydroxypropyl)-4′-ethyl-1,1′-biphenyl-4-carboxamide 372.4 406

4′-ethyl-N-((1R,2R)-1- {[formyl(hydroxy)amino]methyl}-2-hydroxypropyl)-1,1′-biphenyl-4-carboxamide 357.4 407

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(trifluoromethyl)phenyl]ethynyl}benzamide 407.4 408

1,1-dimethylethyl 2-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl) phenyl]carbonyl)amino)propyl]amino}-2-oxoethylcarbamate 481.5 409

N-[(1S)-1-{[(aminoacetyl)amino]methyl)-2- (hydroxyamao)-2-oxoethyl]-4-(phenylethynyl)benzamide 381.4 410

N-[(1S)-1-{[(4-aminobutanoyl)amino]methyl}-2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 409.5 411

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-pent-1-ynylbenzamide 305.3 412

N-{(1S,2R)-2-[(1,1-dimethylethyl)oxy]-1-[(hydroxyamino)carbonyl]propyl)-4′-propyl- 1,1′-biphenyl-4-carboxamide413.5 413

1,1-dimethylethyl (1S)-4-({[(1,1′-dimethylethyl)oxy]carbonyl}amino)-1-{[(2-{4′- [({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino) carbonyl]-1,1′-biphenyl-4-yl}ethyl)amino]carbonyl}butylcarbamate 672.8 414

4′-(2-aminoethyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 358.4 415

4′-(2-{[(2S)-2,5- diaminopentanoyl]amino}ethyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}- 1,1′-biphenyl-4-carboxamide472.6 416

4-(cyclohex-1-en-1-ylethynyl)-N-{(1S,2R)-2- hydroxy-1-[(hydzoxyamino)carbonyl]propyl)benzamide 343.4 417

4-(3,3-dimethylbut-1-ynyl)-N-((1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 319.4 418

N-{(1S)-1-{[(aminoacetyl)amino]methyl)-2-[(2-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2-oxoethyl)amino]-2-oxoethyl}-4-(phenylethynyl)benzamide 728.8 419

4-[(4-{[(2S)-2,5- diaminopentanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 468.5 420

4′-(2-aminoethyl)-N-{(1E)-1- [(hydroxyamino)carbonyl]prop-1-enyl}-1,1′-biphenyl-4-carboxamide 340.4 421

2′,4′-difluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 351.3 422

N-[(1E)-1-formylprop-1-enyl]-4′-propyl-1,1′- biphenyl-4-carboxamide308.4 423

N-hydroxy-4-(pyridin-3-ylethynyl)benzamide 239.2 424

4-(3-hydroxy-3,5-dimethylhex-1-ynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 363.4 425

4′-ethyl-N-{(1R,2R)-2-hydroxy-1-[(hydroxyamino)methyl]propyl}-1,1′-biphenyl- 4-carboxamide 329.4 426

4′-ethyl-N-{(1R,2R)-1- [(hydroxyamino)methyl]-2-[(phenylmethyl)oxy]propyl}-1,1′-biphenyl-4- carboxamide 419.5 427

4′-ethyl-N-[(5R,6R)-3-hydroxy-6-methyl-2-oxo-1,3-oxazinan-5-yl]-1,1′-biphenyl-4- carboxamide 355.4 428

N-((1R,2R)-1-{[({[2- (dimethylamino)ethyl]amino}carbonyl)(hydroxy)amino]methyl}-2-hydroxypropyl)-4′-ethyl- 1,1′-biphenyl-4-carboxamide443.6 429

N-((1R,2R)-1-{[{[(2-cyanoethyl)amino]carbonyl)(hydroxy)amino]methyl)-2-hydroxypropyl)-4′-ethyl-1,1′-biphenyl-4-carboxamide 425.5 430

4′-ethyl-N-((1R,2R)-2-hydroxy-1- {[hydroxy({[3-(2-oxopyrrolidin-2-yl)propyl]amino}carbonyl)amino]methyl}propyl)-1,1′-biphenyl-4-carboxamide497.6 431

(1R,2R)-3-[({[2- (dimethylamino)ethyl]amino}carbonyl)(hydroxy)amino]-2-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-1-methylpropyl 2- (dimethylamino)ethylcarbamate 557.7432

(1R,2R)-3-({[(2- cyanoethyl)amino]carbonyl}(hydroxy)amino]-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-1-methylpropyl 2-cyanoethylcarbamate 521.6 433

N-{(1E)-1-[(E)-(hydroxylmino)methyl]prop-1-enyl)-4′-propyl-1,1′-biphenyl-4-carboxamide 323.4 434

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-(pyridin-3-ylethynyl)benzamide 340.3 435

N-{(1S,2R)-2-hydxoxy-1- [(hydroxyamino)carbonyl]propyl}-4-[3-(methylamino)prop-1-ynyl]benzamide 306.3 436

N-[(1S)-1-[(dimethylamino)methyl]-2-(hydroxyamino)-2-oxoethyl]-4-ethyl-1,1′- biphenyl-4-carboxamide 356.4437

N-[1-(N-hydroxycarbamoylmethyl)(1R,2R)-2- hydroxypropyl][4-(4-ethylphenyl)phenyl]carboxamide 357.4 438

N-[(1S)-1-[(diethylamino)methyl]-2-(hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 384.5439

4-[(3-aminophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 354.4 440

4-[3-(dimethylamino)prop-1-ynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 320.4 441

4-[3-(dimethylamino)prop-1-ynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 320.4 442

4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 411.4 443

3′-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-4′-methyl- 1,1′-biphenyl-4-carboxamide347.4 444

N-[(1S)-1-formyl-2-methylpropyl]-1,1′- biphenyl-4-carboxamide 282.4 445

N-{(1S)-1-[(E)-(hydroxylmino)methyl]-2-methylpropyl}-1,1′-biphenyl-4-carboxamide 297.4 446

N-((1E)-1-{(E)- [(aminocarbonyl)hydrazono]methyl}prop-1-enyl)-4-propyl-1,1′-biphenyl-4-carboxamide 365.4 447

4-[(4-aminophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 354.4 448

4-{[3-(aminomethyl)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 368.4 449

N-(2-aminoethyl)-3-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)amino)carbonyl]phenyl}ethynyl)benzamide425.5 450

N-((1S)-1-{(E)- [(aminocarbonyl)hydrazono]methyl}-2-methylpropyl)-1,1′-biphenyl-4-carboxamide 339.4 451

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)4-{[3-(propanoylamino)phenyl]ethynyl}benzamide 410.4 452

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[3-(morpholin-4-ylmethyl)phenyl]ethynyl}benzamide 438.5 453

4-[(3-{[(2-aminoethyl) amino]methyl)phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.5 454

N-[(1R)-2-(hydxoxyamino)-1-(hydroxymethyl)-2-oxoethyl]-4′-propyl-1,1′-biphenyl-4- carboxamide 343.4 455

N-[1-(N-hydroxycarbamoylmethyl)(1R,2R)-2- hydroxypropyl][4-(2-phenylethynyl)phenyl]carboxamide 353.4 456

4′-ethyl-N-[(1R,2R)-1- [(hydroxyamino)carbonyl]-2-(methyloxy)propyl]-1,1′-biphenyl-4- carboxamide 357.4 457

4′-ethyl-N-[(1S)-1-[(ethylamino)methyl]-2- (hydroxyamino)-2-oxoethyl9-1,1′-biphenyl- 4-carboxamide 356.4 458

4′-ethyl-N-[(1S)-2-(hydroxyamino)-2-oxo-1- ({[(2S)-pyrrolidin-2-ylmethyl]amino)methyl)ethyl]-1,1′-biphenyl-4- carboxamide 411.5 459

[(1S)-1-[(ethylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4-(phenylethynyl)benzamide 352.4 460

N-[(1S)-2-(hydroxyamino)-2-oxo-1-({[(2S)-pyrrolidin-2-ylmethyl]amino}methyl)ethyl]-4- (phenylethynyl)benzamide407.5 461

4′-ethyl-N-((1S)-2-(hydroxyamino)-1-{[(1-methylethyl)amino]methyl}-2-oxoethyl)-1,1′- biphenyl-4-carboxamide 370.5462

4′-ethyl-N-[(1S)-2-(hydroxyamino)-1-{([2-(methylamino)ethyl]amino}methyl)-2-oxoethyl]-1,1′-biphenyl-4-carboxamide 385.5 463

4′-ethyl-N-((1S)-2-(hydroxyamino)-1-([(1-methylpiperidin-4-yl)amino]methyl]-2-oxoethyl)-1,1′-biphenyl-4-carboxamide 425.5 464

N-((1S)-2-(hydroxyamino)-1-{[(1-methylethyl)amino]methyl}-2-axoethyl)-4- (phenylethynyl)benzamide 366.4465

N-[(1S)-2-(hydroxyamino)-1-({[2- (methylamino)ethyl]amino}methyl)-2-oxoethyl]-4-(phenylethynyl)benzamide 381.4 466

N-((1S)-2-(hydroxyamino)-1-{[(1- methylpiperidin-4-yl)amino]methyl}-2-oxoethyl)-4-(phenylethynyl)benzamide 421.5 467

N-[(1S)-1-{[(2-aminoethyl)amino]methyl}-2- (hydroxyamino)-2-oxoethyl]-4-(phenylethynyl)benzamide 367.4 468

N-[(1S)-1-{[bis(2-aminoethyl)amino]methyl}-2-hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 410.5 469

N-((1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(morpholin-4- ylacetyl)amino]phenyl}ethynyl)benzamide 481.5 470

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(propanoylamino)phenyl]ethynyl}benzamide 410.4 471

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(trifluoromethyl)oxy]phenyl}ethynyl) benzamide 423.4 472

1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-{[(4-{[3-(propanoylamino)phenyl]ethynyl}phenyl) carbonyl]amino}propylcarbamate495.5 473

1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-{[(4-pent-1-ynylphenyl)carbonyl]amino}propylcarbamate 390.4 474

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3-(propanoylamino)phenyl]ethynyl}benzamide 395.4 475

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-pent-1-ynylbenzamide 290.3 476

4-(phenyloxy)benzaldehyde thiosemicarbazone 272.3 477

4-(phenyloxy)benzaldehyde semicarbazone 256.3 478

4-{[3-(trifluoromethyl)phenyl]oxy}benzaldehyde thiosemicarbazone 340.3479

4-[(3,4-difluorophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 375.3 480

4-[(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 373.3 481

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-phenylbuta-1,3-diynyl)benzamide 348.4 482

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4′-propyl-1,1′-biphenyl-4-carboxamide 342.4 483

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-1,1′:4′,1″-terphenyl-4-carboxamide 376.4 484

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′:4′,1″-terphenyl-4-carboxamide 391.4 485

1,1-dimethylethyl (2S)-2-[({4-[(4-{[({[(1,1-dimethylethyl)oxy]carbonyl}amino)acetyl]amino)phenyl)ethynyl]phenyl}carbonyl)amino]-3-(hydroxyamino)-3-oxopropylcarbamate 596.6 486

N-[(1S,2R)-1-(hydrazinocarbonyl)-2-hydroxypropyl]-4-(phenylethynyl)benzamide 338.4 487

2-[(2S,3R)-3-hydroxy-2-({[4- (phenylethynyl)phenyl]carbonyl)amino)butanoyl]hydrazinecarboxamide 381.4 488

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(2-methylphenyl)ethynyl]benzamide 353.4 489

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbanyl]propyl}-4-[(3-hydroxyphenyl)ethynyl]benzamide 355.4 490

4-({3-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 411.4 491

4-{[4-({[(cyanomethyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 450.5492

4′-ethyl-N-{(1S)-2-(hydroxyaxruino)-2-oxo-1- [(tetrahydro-2H-pyran-4-ylamino)methyl]ethyl}-1,1′-biphenyl-4- carboxamide 412.5 493

N-{(1S)-2-(hydroxyamino)-2-oxo-1- [(tetrahydro-2H-pyran-4-ylamino)methyl]ethyl}-4- (phenylethynyl)benzamide 408.5 494

4-[(4-chlorophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 373.8 495

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-methylphenyl)ethynyl]benzamide 353.4 496

4-[(2-fluorophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 357.4 497

4-[(3-fluorophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 357.4 498

4-[(4-fluorophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 357.4 499

4-[(4-{[(cyclopropylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 451.5500

4-({4-[({[2-(dimethylamino)ethyl]amino]acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 482.6 501

4-({4-[({[2-(acetylamino)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-[(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 496.5 502

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[3-(2-oxopyrrolidin-1-yl)propyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 536.6 503

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-([4-({[(pyridin-3- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide502.5 504

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2-pyridin-2- ylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide516.6 505

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(4-methylpiperazin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 494.6506

4-({4-[(1,4′-bipiperidin-1′-ylacetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 562.7 507

1-(2-{[4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl)ethynyl)phenyl]amino}-2-oxoethyl)piperidine-4-carboxamide 522.6 508

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl]-4-[(4-{[(piperidin-3-ylamino) acetyl]amino)phenyl)ethynyl]benzamide 494.6 509

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(piperidin-4-ylamino) aceyl]amino}phenyl)ethynyl]benzamide 494.6 510

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(piperidin-2- ylmethyl)amino)acetyl}amino) phenyl]ethynyl}benzamide508.6 511

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-{[4-({[(piperidin-3- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide508.6 512

4-[(4-{[(3-aminopyrrolidin-1-yl)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroyx-1-[(hydroxyamino)carbonyl]propyl}benzamide 480.5 513

4-({4-[(azepan-1- ylacetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 493.6 514

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-{[4-({[(4-morpholin-4- ylphenyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 572.6515

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2-hydroxyethyl)amino]acetyl}amino)phenyl]ethnyl}benzamide 440.5 516

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cyclopropylamino)acetyl]amino}phenyl)ethynyl]benzamide 436.5 517

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({[3-(2-oxopyrrolidin-1-yl)propyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 521.6 518

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)ethynyl]benzamide 479.6 519

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(pyridin-3- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 487.5 520

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(piperidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide464.5 521

4-{[4-({[(2-hydroxyethyl) amino]acetyl}amino)phenyl]ethnyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 455.5522

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 469.5 523

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({methyl[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 483.5 524

4-{[4-({[[2-(dimethylamino) ethyl](methyl)amino]acetyl}amino)phenyl]ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 496.6 525

4-{[4-({[(3R)-3-(dimethylamino)pyrrolidin-1-yl]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydxoxyamino)carbonyl]propyl}benzamide 508.6 526

4-{[4-({[(3S)-3-dimethylamino)pyrrolidin-1-yl]acetyl)amino)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)benzamide 508.6 527

4-{[4-({[(3R)-3-(acetylamino)pyrrolidin-1-yl]acetyl)amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)benzamide 522.6 528

4-{[4-({[(3S)-3-(acetylamino)pyrrolidin-1-yl]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 522.6 529

4-{[4-({[(3R)-1-azabicyclo[2.2.2]oct-3-ylamino]acetyl}anxino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 520.6 530

4-{[4-({[(3S)-1-azabicyclo[2.2.2]oct-3-ylamino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 520.6 531

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-({4-[({[(2R)-pyrralidin-2-ylmethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 494.6 532

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-({4-[({[(2S)-pyrrolidin-2-ylmethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 494.6 533

4-{[4-({[(3-aminocyclohexyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 508.6 534

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(3-hydroxypiperidin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 495.5 535

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbanyl]propyl}-4-{[4-({[(3-morpholin-4-ylpropyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 538.6536

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2-methylpropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 467.5 537

4-[(4-{[(ethylamino)acetyl]amino)phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5538

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-({4-[(piperidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide 479.5 539

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(3-hydroxypropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 469.5 540

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-({4-[({[3-(methyloxy)propyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 483.5 541

4-{[4-({[(2-cyanoethyl) amino]acetyl}amino)phenyl]ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.5542

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2-pyrrolidin-1-ylethyl)amino]acetyl) amino)phenyl]ethynyl}benzamide 508.6543

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}4-[(4-{[(2-methyl-1H-imidazol-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 476.5 544

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(methylamino)acetyl]amino}phenyl)ethynyl]benzamide 410.4 545

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2-methylpropyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 452.5 546

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 454.5 547

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({methyl[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 468.5 548

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(3-hydroxypropyl)amino]acetyl}amino)phenyl]ethynyl)benzamide 454.5 549

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[3-(methyloxy)propyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 468.5 550

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[2-(dimethylamino)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 467.5551

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[2-(dimethylamino)ethyl](methyl)amino]acetyl)amino)phenyl]ethynyl}benzamide481.6 552

4-({4-[(}[2-(acetylamino)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 481.5 553

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2-cyanoethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 449.5 554

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2-pyrrolidin-1-ylethyl)amino]acetyl}amino)phenyl]ethynyl)benzamide 493.6 555

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl}-4-({4-[({[4-(dimethylamino)butyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 495.6556

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(morpholin-4- ylacetyl)amino]phenyl}ethynyl)benzamide466.5 557

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(azepan-1-ylacetyl)amino]phenyl}ethynyl)benzamide 478.6 558

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(pyrrolidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide450.5 559

1-{2-[(4-{[4-({[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]amino)carbonyl)phenyl]ethynyl}phenyl)amino]-2-oxoethyl}piperidine-4- carboxamide 507.6 560

4-{[4-({[(3R)-3-(acetylamino)pyrralidin-1-yl]acetyl]amino)phenyl]ethynyl}-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxaethyl]benzamide 507.6 561

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(3R)-3-(dimethylamino)pyrrolidin-1- yl]acetyl) amino)phenyl]ethynyl}benzamide493.6 562

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(3-aminopyrralidin-1-yl)acetyl]amino}phenyl)ethynyl]benzamide 465.5 563

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(piperidin-3-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 479.6 564

N-[(1S)-1-(aminoznethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(piperidin-4-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 479.6 565

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{(4-({[(piperidin-2-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 493.6 566

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(piperidin-3-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 493.6 567

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(pyridin-2-ylmethyl)amino]acetyl}amino)phenyl]ethyayl}benzamide 487.5 568

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(pyridin-4-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 487.5 569

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2-pyridin-2-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 501.6 570

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2-pyridin-3-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 501.6 571

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2-pyridin-4-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 501.6 572

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(phenylamino) acetyl]amino}phenyl)ethynyl]benzamide472.5 573

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-([4-({[(phenylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 486.5 574

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2-phenylethyl)amino]acetyl]amino)phenyl]ethynyl}benzamide 500.6 575

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(1H-imidazol-1- ylacetyl)amino]phenyl}ethynyl)benzamide447.5 576

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(1H-imidazol-1- ylacetyl)amino]phenyl}ethynyl)benzamide 462.5 577

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(phenylamino)acetyl]amino}phenyl) ethynyl]benzamide 487.5 578

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2-phenylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 515.6 579

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(3-phenylpropyl)amino]acetyl}amino) phenyl]ethnyl}benzamide 529.6 580

4-[(3-{[(aminoacetyl)amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 425.5 581

4-[(2-aminopyrimidin-5-yl)ethynyl]-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 356.4 582

4-{(4-acetylphenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 381.4 583

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({2-[4-(phenylmethyl)piperazin-1-yl]ethyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 613.7 584

4-{[4-({[(aminoacetyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 468.5585

4-{[4-({[4-(2-hydroxyethyl)piperazin-1-yl]acetyl}amino)phenyl]ethynyl)-N-{(1S,2R)- 2-hydxoxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 524.6 586

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{(4-[({(3R)-3-[(trifluoroacetyl)amino]pyrrolidin-1-yl}acezyl)amino]phenyl}ethynyl)benzamide 576.5 587

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(methylamino)acetyl]amino}phenyl)ethynyl]benzamide 425.5 588

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(piperazin-1-ylacetyl) amino]phenyl}ethynyl)benzamide 480.5 589

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl{-4-{[4-({[(pyridin-2-ylmethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide502.5 590

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(pyridin-4- ylmethyl)amino]acetyl}amino)pheuyl]ethynyl}benzamide502.5 591

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl)propyl)-4-{(4-({[(2-pyridin-3- ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 516.6 592

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2-pyridin-4- ylethyl)amino]acetyl}amino)pheuyl]ethynyl}benzamide 516.6 593

4-({4-[({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 519.5 594

4-({4-[({[(2-chloropheuyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 536.0 595

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[{[2-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide531.6 596

4-({4-[({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 519.5 597

4-({4-[({[(3-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 536.0 598

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[3-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide531.6 599

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[{[(3-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 515.6600

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[3-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide569.5 601

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{(4-({[({3-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide585.5 602

4-({4-[({[(4-fluorophenyl)methyl]amino}acctyl]amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 519.5 603

N-{(1S,2R)-2-hydroxy-1- [hydroxyamino)carbonyl]propyl}-4-({4-[({[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 515.6604

4-[(4-{[({[4-(dimethylamino)phenyl]methyl}amino)acelyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 544.6 605

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[4-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide569.5 606

4-[(4-{[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 587.5 607

4-({4-[({[(2,4-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 537.5 608

4-({4-[({[(2,4-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 570.4 609

4-{[4-({[(2-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 505.5610

4-{[4-({[(4-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 505.5611

4-({4-[({[(3,5-difluorophenyl)methyl]amino)acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 537.5 612

4-{[4-({[(4-bromophenyl)amino]acetyl}amino)phenyl]ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 566.4 613

4-({4-[({[4-(dimethylamino)phenyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 530.6 614

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2S)-2-aminopropanoyl]amino}phenyl)ethynyl]benzamide 410.4 615

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2R)-2-aminopropanoyl]amino}phenyl)ethynyl]benzamide 410.4 616

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(2S)-2-amino-4- methylpentanoyl]amino}phenyl)ethynyl]benzamide 452.5 617

4-[(4-{[(2S,3R)-2-amino-3- hydroxybutanoyl]amino}phenyl)ethynyl]-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]benzamide 440.5 618

4-[(4-{[(2S)-2-amino-4- cyanobutanoyl]amino}phenyl)ethynyl]-N-[(1S)-1-(amnomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 449.5 619

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2S)-2,3-diaminopropanoyl]amino}phenyl) ethynyl]benzamide 425.5 620

(2S)-N-(4-([4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl)pyrrolidine-2-carboxamide436.5 621

(2S)-N-(4-{[4-({[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl)piperidine-2-carboxamide 450.5 622

N-(4-{[4-({[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl)piperidine-3-carboxamide 450.5 623

4-[(4-{[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino}phenyl)ethynyl]-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 476.5 624

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-methylphenyl) ethynyl]benzamide 338.4 625

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(2-fluorophenyl)ethynyl]benzamide 342.3 626

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(3-fluorophenyl)ethynyl]benzamide 342.3 627

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-fluorophenyl)ethynyl]benzamide 342.3 628

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-chlorophenyl)ethynyl]benzamide 358.8 629

4-[(4-{[(2S)-2-amino-4-methylpentanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 467.5 630

4-[(4-{[(2S)-2-amino-4- cyanobutanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.5 631

4-[(4-{[(2S)-2,3- diaminopropanoyl]amino}pheriyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 440.5 632

N-[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl) phenyl]piperidine-3-carboxamide 465.5 633

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-({3-[(morpholin-4-ylacetyl) amino]phenyl}ethynyl)benzamide 481.5 634

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-(pyrazin-2-ylethynyl)benzamide 341.3 635

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[3-(1H-imidazol-1-yl)propyl]amino}acetyl)amino]phenyl)ethynyl)benzamide519.6 636

N-((1S)-2-(hydroxyamino)-1-{[({[3-(1H-imidazol-1-yl)propyl]amino}acetyl)amino]methyl}-2-oxoethyl)-4-(phenylethynyl)benzamide 489.5 637

4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)benzoicacid 383.4 638

N-(2-{[4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)pheayl]amino}-2-oxoethyl)-1,3-benzodioxole-4-carboxamide 559.5 639

4-({4-[((2R)-2-{[(2R)-2,5- diaminopentanoyl]amino}-4-phenylbutanoyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 629.7 640

4-[(4-{[(2R)-2-amino-4- phenylbutanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 515.6 641

4-[(4-{[(2S)-2-amino-3- phenylpropanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 501.6 642

4-{[4-({[(2-aminoethyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)benzamide 454.5643

N-{(1S)-2-(hydroxyamino)-1-[({[methyl(1-methylpiperidin-4-yl)amino]acetyl}amino)methyl]-2-axoethyl}-4-(phenylethynyl)benzamide 492.6 644

4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 465.5 645

4-[(4-{[(cyclopentylamino)acetyl]amino}phenylethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 479.5 646

4-[(4-{[(cyclohexylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 493.6 647

4-[(4-{[(cycloheptylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 507.6 648

4-[(4-{[(cyclooctylamino)acetyl]amino)phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 521.6 649

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(propylamino)acetyl]amino}phenyl)ethynyl]benzamide 453.5 650

4-[(4-{[(hexylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbanyl]propyl}benzamide 495.6 651

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(1-methylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 453.5 652

4-{[4-({[(1,1-dimethylethyl)amino]acetyl}amino)phenyl]ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 467.5653

4-{[4-({[ethyl(methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 453.5 654

4-[(4-{[(diethylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 467.5 655

4-{[4-({[(1,1-dimethylethyl)(methyl)amino]acezyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 481.6 656

4-{[4-({[cyclohexyl(methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 507.6 657

4-{[4-({[bis(1-methylethyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 495.6 658

4-{[4-({[(cyclohexylmethyl)amino]acetyl]amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 507.6659

4-{[4-({[(2,3-dimethylcyclohexyl)amino]acetyl}amino)phenyl]ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 521.6 660

4-{[4-({[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 505.6 661

4-[(4-[[({[(1S,2R,5S)-6,6- dimethylbicyclo[3.1.1]hept-2-yl]methyl)amino}acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 547.7 662

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[4-(trifluoromethyl)piperidin-1- yl]acetyl}amino)phenyl]ethynyl}benzamide547.5 663

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 504.5 664

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 521.0665

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2-methylphenyl)methyl]amino}acctyl)amino]phenyl}ethynyl)benzamide 500.6666

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[2-(methyloxy)phenyl]methyl}amino) acetyl]amino}phenyl)ethynyl]benzamide516.6 667

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[2-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide554.5 668

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 570.5 669

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 504.5670

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 521.0671

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 500.6672

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[{[3-(methyloxy)phenyl]methyl}amino) acetyl]amino}phenyl)ethynyl]benzamide516.6 673

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[3-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide554.5 674

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[({3-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide570.5 675

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(4-fluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 504.5676

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(4-chlorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 521.0

Example Structure Name MH+ 677

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 500.6678

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide516.6 679

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4-(trifluoromethyl)phenyl]methyl}amino)acelyl]amino}phenyl)ethynyl]benzamide554.5 680

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide542.6 681

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(1R)-1-phenylethyl]amino}acctyl)amino]phenyl}ethyl)benzamide 500.6 682

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(1S)-1-phenylethyl]amino}acetyl)amino]phenyl}ethyl)benzamide 500.6 683

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(cyclohexylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 492.6684

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cyclobutytamino)acetyl]amino}phenyl) ethynyl]benzamide 450.5 685

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cyclopentylamino)acetyl]amino}phenyl) ethynyl]benzamide 464.5 686

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cyclohexylamino)acetyl]amino}phenyl) ethynyl]benzamide 478.6 687

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cycloheptylamino)acetyl]amino}phenyl) ethynyl]benzamide 492.6 688

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cyclooctylamino)acetyl]amino}phenyl) ethynyl]benzamide 506.6 689

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(ethylamino)acetyl]amino}phenyl)ethynyl]benzamide 424.5 690

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(propylamino)acetyl]amino}phenyl)ethynyl]benzamide 438.5 691

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(butylamino)acetyl]amino}phenyl)ethynyl]benzamide 452.5 692

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(hexylamino)acetyl]amino}phenyl)ethynyl]benzamide 480.6 693

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1-methylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 438.5 694

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1,1-dimethylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 452.5 695

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[ethyl(methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 438.5 696

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(diethylamino)acetyl]amino}phenyl)ethynyl]benzamide 452.5 697

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{(4-({[(1,1-dimethylethyl)(methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 466.6698

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[cyclohexyl(methyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 492.6699

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[2-(2-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzarnide 518.6700

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[2-(3-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 701

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[2-(4-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 702

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({[(1S,2R)-2-phenylcyclopropyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 512.6 703

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,4-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 522.5704

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,4-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.4705

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide572.5 706

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,5-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 522.5707

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl)-4-({4-[({[(3,4-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 522.5708

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3,4-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.4709

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3,4-dimethylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 514.6710

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3,5-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 522.5711

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3,5-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.4712

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[3,5-bis(trifluoromethyl)phenyl]methyl}amino)acetyl]amino)phenyl)ethynyl]benzamide 622.5 713

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(4-nitrophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 531.5 714

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-2-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 473.5 715

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-3-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 473.5 716

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 490.5 717

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(3-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 490.5 718

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl)-4-{[4-({[(4-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 490.5 719

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-4-ylamino)acetyl]amino)phenyl)ethynyl]benzamide 473.5 720

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2,2,2-trifluoroethyl)amino]acetyl}amino)phenyl]ethnyl}benzamide 478.4 721

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(4-{[(pyridin-2-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 488.5 722

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(4-{[(pyridin-3-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 488.5 723

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(4-{[(pyridin-4-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 488.5 724

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(4-phenylpiperazin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 556.6 725

4-{[-({[4-(4-fluorophenyl)piperazin-1-yl]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 574.6 726

4-{[4-({[(1-acetylpiperidin-4-yl)(cyclopropyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 576.7 727

4-[(4-{[(butylamino) acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 467.5728

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(1R)-1- phenylethyl]amino}acetyl)amino]phenyl]ethynyl)benzamide515.6 729

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(1S)-1- phenylethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide515.6 730

4-{[4-({[cyclopropyl(methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)caxbonyl]propyl}benzazmde 465.5 731

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[methyl(phenylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide515.6 732

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[cyclopropyl(methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 450.5733

4-[(4-{[(2S)-2- aminopropanayl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 425.5 734

4-[(4-{[(2R)-2- aminopropanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbanyl]propyl}benzamide 425.5 735

4-{(4-{[(2S)-2-amino-3- methylbutanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 453.5 736

4-{(4-{[(2S,3R)-2-amino-3- hydroxybutanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 455.5 737

(2S)-N-[4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]pyrrolidine-2-carboxamide 451.5 738

4-[(4-{[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 491.5 739

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(methyloxy)acetyl]amino}phenyl)ethynyl]benzamide 426.4 740

4-[(4-{[(2S)-2-amino-3- methylbutanoyl]amino}phenyl)ethynyl]-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 438.5 741

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(3-phenylpropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 514.6 742

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(thien-2-ylethynyl)benzamide 345.4 743

4-({4-[((2S)-2-{[(2S)-2,5- diaminopentanoyl]amino}-3-phenylpropanoyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 615.7 744

3,4-dihydroxy-N-[(2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl)phenyl]caxbonyl}amino)propyl]benzamide 460.5 745

1,1-dimethylethyl 3-[(2-{[(2S)-3- (hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2-oxoethyl)amino]propylcarbamate538.6 746

N-[(1S)-2-(hydroxyamino)-1-({[(4-methylpiperazin-1-yl)acetyl]amino)methyl)-2-oxoethyl]-4-(phenylethynyl)benzamide 464.5 747

4-{[4-({2-[(2-aminoethyl)amino]-2-oxoethyl}oxy)phenyl]ethynyl)-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 455.5 748

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3-(aminomethyl)phenyl]ethynyl}benzamide 353.4 749

1,1-dimethylethyl (2S)-3-(hydxoxyamino)-2-[({4-[(4-([2-(hydroxyamino)-2-oxoethyl]oxy}phenyl)ethynyl]phenyl}carbonyl]amino]-3-oxopropylcarbamate513.5 750

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[2-(hydroxyamino)-2-oxoethyl]oxy}phenyl)ethynyl]benzamide 413.4 751

3,4-dihydroxy-N-(2-{[4-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]amino}-2-oxoethyl)benzamide 547.5 752

4-({4-[({[(2S)-2,5-diaminopentanoyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 525.6 753

4-[(4-{[(2- aminoethyl)amino]carbonyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 425.5754

N-[(1S)-1-[({[(3- aminopropyl)amino]acetyl}amino)methyl]-2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 438.5 755

3-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)benzoic acid 383.4 756

4-{[4-({[(3-aminopropyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-bydroxy-1- [(hydroxyamino)caxbonyl]propyl}benzamide 468.5757

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(pyrazin-2-ylethynyl)benzamide 326.3 758

4-({3-[(4-aminobutanoyl) amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]benzamide 424.5 759

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2S)-2,5-diaminopentanoyl]amino}phenyl)ethynyl]benzamide 453.5 760

4-({2-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 396.4 761

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[2-(ethylamino)-2- oxoethyl]phenyl}ethynyl)benzamide409.5 762

4-({4-[(aminoacetyl)amino]-3- methylphenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 410.4 763

4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-3-fluorobenzamide414.4 764

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(cyanomethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 435.5 765

[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]acetic acid 397.4 766

4-amino-2-({[4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]carbonyl)amino)-4-oxobutanoic acid 497.5767

4-amino-2-[({[4-({4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]oxy}acetyl)amino]-4-oxobutanoic acid527.5 768

N-((1S)-2-(hydroxyamino)-1-{[(morpholin-4-ylacetyl)amino]methyl}-2-oxoethyl)-4- (phenylethynyl)benzamide 451.5 769

N-[(1S)-1-[({[(2,3-dihydroxypropyl) thio]acetyl}amino)methyl]-2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 472.5 770

methyl (2S).3-amino-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)propanoate 323.4 771

N-{(1S)-2-(hydroxyamino)-2-oxo-1-[({[(2- phenylethyl)amino]acetyl}amino)methyl]ethyl}-4-(phenylethynyl)benzamide 485.6 772

4-[(4-(2-[(2-aminoethyl)amino]-2- oxoethyl}phenyl)cthynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5 773

4-[(4-{[(6-aminohexyl) amino]carbonyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 481.6774

4-[4-(4-{[(ethylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide463.5 775

4-[4-(4-{[(cyclopropylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzaznide 475.5 776

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[(piperidin-1-ylacetyl)amino]phenyl}buta-1,3-diynyl)benzamide 503.6 777

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4-{[(phenylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 511.5 778

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(phenylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide525.6 779

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl)-4′-ethyl-1,1′-biphenyl-4-carboxamide 342.4 780

4-[(4-{[(dimethylamino) acetyl]amino}phenyl)ethynl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5781

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(pyrrolidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide 465.5 782

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(pentylamino)acetyl]amino}phenyl)ethynyl]benzamide 481.6 783

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-{[4-({[(thien-2-ylmethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 507.6784

4-{[4-({[(1H-benzimidazol-2-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbanyl]propyl}benzamide 541.6 785

4-{[4-({[[(1-benzothien-3- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 557.6786

4-(4-{4-[({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 543.6 787

4-(4-{4-[({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 543.6 788

4-(4-{5-[({[(4-fluoropheixyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 543.6 789

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4-(4-{4- [({[(2-methylphenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3-diynyl)benzamide539.6 790

N-{(1S,2R)-2-hydroxy-1- [(hydxoxyamino)carbonyl]propyl)-4-(4-{4- [({[(3-methylphenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3-diynyl)benzamide539.6 791

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-(4-{4- [({[(4-methylphenyl)methyl]amino}acctyl) amino]phenyl}buta-1,3-diynyl)benzamide539.6 792

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(pyridin-2-ylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 526.6 793

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(pyridin-3-ylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 526.6 794

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(pyridin-4-ylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 526.6 795

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[4-(4- {[({[2-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 555.6 796

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[({[3-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 555.6 797

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 555.6 798

4-{4-[4-({[(2-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide529.5 799

4-{4-[4-({[(3-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 529.5 800

4-{4-[4-({[(4-fluorophenyl) amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 529.5 801

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4-{[(pyridin-2- ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide512.5 802

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[4-(4-{[(pyridin-3- ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide512.5 803

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4-{[(pyridin-4- ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide512.5 804

4-[4-(4-{[(cyclobutylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl)propyl}benzamide 489.5 805

4-[4-(4-{[(cyclopentylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 503.6 806

4-[4-(4- {[(cyclobexylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 517.6 807

4-[4-(4-{[(cyclaheptylamino)acetyl]amino}phenyl)buta1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 531.6 808

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]prapyl}-4-[4-(4-{[(methylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 449.5 809

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbanyl]propyl}-4-[4-(4-{[(propylamino)acetyl]amino)phenyl)buta-1,3- diynyl]benzamide 477.5 810

4-[4-(4- {[(butylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide491.6 811

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4-{[(pentylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 505.6 812

4-[4-(4- {((hexylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide519.6 813

4-{4-[4-({[ethyl(methyl)amino]acetyl)amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydxoxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 477.5 814

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(1-methylethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide477.5 815

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(2-methylpropyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide491.6 816

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4-({[(2,2,2-trifluoroethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 517.5 817

4-{4-[4-({[(2- hydroxyethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 479.5 818

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[({[2-(methyloxy)ethyl]amino)acetyl)amino]phenyl}buta-1,3-diynyl)benzamide493.5 819

4-(4-{4-[({[2-(dimethylamino)ethyl]amino)acetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydxoxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 506.6 820

4-{4-[4-({[(2-cyanoethyl) amino]acetyl}amino)phenyl]buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 488.5 821

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[(pyrrolidin-1-ylacetyl)amino]phenyl)buta-1,3- diynyl)benzamide 489.5822

4-(4-{4-[(azepan-1- ylacetyl)aminolphenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 517.6 823

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4-{[(4-methylpiperazin-1- yl)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide518.6 824

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4-(4-{4-[(morpholin-4-ylacetyl)amino]phenyl)buta-1,3- diynyl)benzamide 505.5 825

4-{4-[4-({[cyclohexyl(methyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 531.6 826

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[({[(1R)-1-phenylethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6827

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[({[(1S)-1- phenylethyl]amino)acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6 828

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4- ({[(2-phenylethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 539.6829

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[(1H-imidazol-1-ylacetyl)amino]phenyl}buta- 1,3-diynyl)benzamide 486.5830

4-{4-[4-({[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 529.6 831

4-{4-[4-({[(cyclohexylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 531.6 832

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4′-ethyl-2-fluoro-1,1′-biphenyl-4- carboxamide 346.4 833

4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-3- (methyloxy)benzamide 441.5 834

4′-ethyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2-(methyloxy)-1,1′-biphenyl-4-carboxamide 373.4 835

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-(methyloxy)-4-(phenylethynyl)benzamide 369.4 836

4-[(4-ethylphenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 367.4 837

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-hydroxyphenyl)ethynyl]benzamide 355.4 838

2-[(2-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbanyl)amino)propyl]amino}-2-oxoethyl)thio]propanoicacid 470.5 839

4-amino-2-[(2-([(2S)-3-(hydroxyamino)-3-oxo- 2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2-oxoethyl)amino]-4-oxobutanoicacid 496.5 840

1,1-dimethylethyl 4-amino-2-[(2-{[(2S)-3- (hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2-oxoethyl)amino]-4-oxobutanoate552.6 841

2,6-dihydroxy-N-[(2S)-3-(hydroxyamino)-3- oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino) propyl[pyridine-4-carboxamide461.4 842

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-aminophenyl)ethynyl]benzamide 339.4 843

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-ethylphenyl)ethynyl]benzamide 352.4 844

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-ethylphenyl)ethynyl]-3- fluorobenzamide 370.4 845

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(3-aminopropanayl)amino]phenyl}ethynyl) benzamide 410.4 846

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(dimethylamino)acetyl]amino}phenyl) ethynl]benzamide 424.5 847

4-({4-[(4- aminobutanoyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 424.5 848

N-{(1S)-2-(hydroxyamino)-1-[({[2-(methyloxy)phenyl]methyl}amino)methyl]-2-oxoethyl}-4-(phenylethynyl)benzamide 444.5 849

N-[(1S)-1-[(diprop-2-enylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4-(phenylethynyl)benzamide 404.5 850

N-[(1S)-2-(hydroxyamino)-1-({[({[2-(methyloxy)phenyl]methyl}amino)acetyl]amino}methyl)-2-oxoethyl]-4-(phenylethynyl)benzamide 501.6 851

N-((1S)-2-(hydroxyamino)-1-{[({[2-(methyloxy)phenyl]thio}acetyl)amino]methyl}-2-oxoethyl)-4-(phenylethynyl)benzamide 504.6 852

(2S,3R)-3-amino-2-({[4-(phenylethynyl)phenyl]carbonyl}amino) butanoicacid 323.4 853

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(dimethylamino)acetyl]amino}phenyl)buta- 1,3-diynyl]benzamide 448.5854

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(ethylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 448.5 855

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclopropylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 460.5856

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[(piperidin-1- ylacetyl)amino]phenyl)buta-1,3-diynyl)benzamide 488.6 857

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(phenylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 496.5 858

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(phenylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide510.6 859

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(4-aminophenyl)buta-1,3- diynyl]benzamide 363.4 860

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(pyrazin-2-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 489.5 861

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(4-phenylpiperidin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 555.6 862

4-{[4-({[4-(2-fluorophenyl)piperazin-1-yl]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 574.6 863

4-{[4-({[(1S,4R)-bicyclo[2.2.1]hept-2-ylamino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 505.6 864

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(1S,2S,3S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept-3-yl]amino}acetyl)amino]phenyl}ethynyl)benzamide 547.7 865

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{(4-({[(tricyclo[3.3.1.1˜3,7˜]dec-1-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 559.7 866

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(4-methylcyclohexyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 507.6 867

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2,2,2- trifluoroethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide493.5 868

4-({4-[({[2-(2-fluorophenyl)ethyl]amino}acetyl]amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 533.6 869

4-({4-[({[2-(3- fluorophenyl)ethyl]amino}acetyl]amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 870

4-({4-[({[2-(4-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 533.6 871

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl]-4-({4-[({[(1S,2R)-2-phenylcyclopropyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 527.6 872

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 515.6873

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[2-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide569.5 874

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide585.5 875

4-({4-[({[(4-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbanyl]propyl}benzamide 536.0 875

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide531.6 877

4-[(4-{[({[5-(1,1-dimethylethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 557.7 878

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({-[({[(4-nitrophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 546.5 879

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide585.5 880

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[4-(methylthio)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide547.6 881

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[({4-[(trifluoromethyl)thio]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide601.6 882

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[{[4-(methylsulfonyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide579.6 883

4-({4-[({[(2,5-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)caxbonyl]propyl}benzamide 537.5 884

4-({4-[({[(2,6-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 537.5 885

4-({4-[({[(3,4-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 537.5 886

4-({4-[({[(3,4-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 529.6 887

4-({4-[({[(3,4-dimethylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 529.6 888

4-({4-[({[(3,5-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 570.4 889

4-[(5-{[({[(3,5- bis(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phcnyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 637.5 890

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-({4-[({[(2,3,4-trifluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.5891

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(2,4,5-trifluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzarmde 555.5892

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(3,4,5-trifluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.5893

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl}-4-[(4-{[(pentylamino)acetyl]amino}phenyl)ethynyl]benzamide 466.6 894

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(thien-2-ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 492.6 895

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(4-phenylpiperidin-1-yl)acetyl]amino}phenyl)ethynyl]benzamide 540.6 896

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(4-phenylpiperazin-1-yl)acetyl]amino}phenyl)ethynyl]benzamide 541.6 897

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[4-(2-fluorophenyl)piperazin-1- yl]acetyl}amino)phenyl]ethynyl}benzamide 559.6898

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[4-(4-fluorophenyl)piperazin-1- yl]acetyl}amino)phenyl]ethynyl}benzamide 559.6899

4-{[4-({[(1-acetylpiperidin-4-yl)(cyclopropyl)amino]acetyl}amino)phenyl]ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide 561.7 900

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2,3-dimethylcyclohexyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 506.6 901

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(1R,2R,4S)- bicyclo[2.2.1]hept-2-ylamino]acetyl}amino)phenyl]ethynyl)benzamide 490.6 902

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[({[(1S,2R,5S)-6,6- dimethylbicyclo[3.1.1]hept-2-yl]methyl}amino)acetyl]amino}phenyl) ethynyl]benzamide 532.7 903

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1S,4R)-bicyclo[2.2.1]hept-2- ylamino]acetyl}amino)phenyl]ethynyl}benzamide490.6 904

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({[(1S,2S,3S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept-3-yl]amino}acetyl)amino]phenyl}ethynyl)benzamide 532.7 905

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(tricycla[3.3.1.1˜3,7˜]dec-1-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 544.7 906

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,6-difluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 522.5907

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4-(methylthio)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide532.6 908

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4-(methylsulfonyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 564.6 909

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[({4-[(trifluoromethyl)thio]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide586.6 910

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide570.5 911

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,4,5-trifluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide540.5 912

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,3,4-trifluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide540.5 913

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3,4,5-trifluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide540.5 914

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[(pyrrolidin-1- ylacetyl)amino]phenyl}buta-1,3-diynyl)benzamide 474.5 915

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[(azepan-1- ylacetyl)amino]phenyl}buta-1,3-diynyl)benzamide 502.6 916

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[(piperazin-1- ylacetyl)amino]phenyl}buta-1,3-diynyl)benzamide 489.5 917

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(4-{[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 503.6 918

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[(morpholin-4- ylacetyl)amino]phenyl}buta-1,3-diynyl)benzamide 490.5 919

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-(4-({[cyclohexyl(methyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 516.6 920

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide528.6 921

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide528.6 922

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(4-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide528.6 923

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide524.6 924

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(3-methylphenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide524.6 925

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide524.6 926

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-({[(pyridin-2-ylmethyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}benzamide 511.6 927

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-({[(pyndin-3- ylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 511.6 928

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-({[(pyridin-4-ylmethyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}benzamide 511.6 929

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[({[2-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide540.6 930

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-([({[3-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide540.6 931

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide540.6 932

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{(4-[4-({[(2-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 514.5933

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(3-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 514.5934

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(4-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 514.5935

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(4-{[(pyridin-2- ylamino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 497.5 936

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(4-{[(pyridin-3- ylamino)acctyl]amino}phenyl)buta-1,3-diynyl]benzamide 497.5 937

N-[(1S)-1-(aminomethyl)-2-(hydroyxamino)-2-oxoethyl]-4-[4-(4-{[(pyridin-4- ylamino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 497.5 938

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclobutylamino)acetyl]amino}phenyl)buta- 1,3-diynyl]benzamide 474.5939

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclopentylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 488.6940

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclohexylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 502.6941

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cycloheptylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 516.6942

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(methylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 434.5 943

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(propylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 462.5 944

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(butylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 476.5 945

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(pentylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 490.6 946

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(hexylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 504.6 947

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[ethyl(methyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide462.5 948

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(1-methylethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 462.5949

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2-methylpropyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 476.5950

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2-hydroxyethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 464.5951

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-{4-[({[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide478.5 952

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[2-(dimethylamino)ethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide491.6 953

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2-cyanoethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 473.5 954

N-[(1S)-1-(aminomethyl)-2-(hydxoxyamino)-2-oxoethyl]-4-{4-[4-({[(thien-2-ylmethyl)amino]acetyl)amino)phenyl]buta-1,3- diynyl}benzamide 516.6 955

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[({[(1R)-1-phenylethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 524.6956

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[({[(1S)-1-phenylethyl]amino}acezyl)amino]phenyl)buta- 1,3-diynyl)benzamide 524.6957

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2-phenylethyl)amino]acetyl}amino)phenyl]buta- 1,3-diynyl}benzamide 524.6958

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-{4-[(1H-imidazol-1- ylacetyl)amino]phenyl}buta-1,3-diynyl)benzamide 471.5 959

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-{4-({[(1R,2R,4S)- bicyclo[2.2.1]hept-2-ylamino]acetyl}amino)phenyl]buta-1,3- diynyl}benzamide 514.6 960

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(cyclohexylmethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 516.6 961

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(6-piperidin-1-ylpyridin-3-yl)ethynyl]benzamide 423.5 962

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[6-(4-methylpiperazin-1-yl)pyridin-3- yl]ethynyl}benzamide 438.5 963

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(6-piperazin-1-ylpyridin-3-yl)ethynyl]benzamide 424.5 964

4-[(6-azepan-1-ylpyridin-3-yl)ethynyl]-N- {(1S,2R)-2-hydroxyl-1-[(hydroxyamino)carbonyl]propyl}benzamide 437.5 965

4-{[6-(cyclobutylamino)pyridin-3-yl]ethynyl}- N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 409.5 966

4-{[6-(cyclohexylamino)pyridin-3-yl]ethynyl}- N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbanyl]propyl}benzamide 437.5 967

4-{[(6-(butylamino)pyridin-3-yl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 411.5 968

4-({6-[(2-hydroxyethyl)amino]pyridin-3-yl}ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 399.4 969

4-[(6-{[2-(dimethylamino)ethyl]amino}pyridin-3-yl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 426.5 970

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({6-[(phenylmethyl)amino]pyridin-3- yl}ethynyl)benzamide 445.5 971

4-[(6-{[(4-fluorophenyl)methyl]amino}pyridin-3-yl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 463.5 972

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[6-(pyridin-4-ylamino)pyridin-3- yl]ethynyl}benzamide 432.4 973

4-[(6-chloropyridin-3-yl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 374.8 974

1,1-dimethylethyl (2S)-2-[({4-[(4-ethylphenyl)ethynyl]phenyl}carbonyl)amino]-3-(hydroxyamino)-3-oxopropylcarbaniate 452.5 975

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]buta-1,3- diynyl)benzamide 493.5 976

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-([4-(morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 438.5 977

4-[(4-{[(2-aminoethyl) amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.5 978

4-({4-[((2S)-2-amino-5-{[amino(imino)methyl]amino}pentanoyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide 495.6 979

(2S)-6-amino-2-({[4-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]carbonyl}amino)hexanoic acid 511.5 980

(2S)-6-amino-2-({[4-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]acetyl}amino)hexanoic acid 525.6 981

5-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino) propyl]amino}-5-oxopentanoic acid438.4 982

N-(2-aminoethyl)-N′-[(2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino) propyl]pentanediamide 480.5 983

N-[(1S)-1-[(2,6-dioxopiperidin-1-yl) methyl]-2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 420.4 984

N,N′-bis[(25)-3-(hydroxyamino)-3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino) propyl]pentanediamide 743.8 985

N-((1S)-2-(hydroxyamino)-2-oxo-1-{[({[(1S)-1-phenylethyl]amino}acetyl)amino]methyl}ethyl)-4-(phenylethynyl)benzamide485.6 986

N-{(1S)-2-hydroxy-1- [(hydroxyamino)carbonyl]-2-methylpropyl}-4-(phenylethynyl)benzamide 353.4 987

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(6-piperidin-1-ylpyndin-3- yl)ethynyl]benzamide 408.5 988

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(6-morpholin-4-ylpyridin-3- yl)ethynyl]benzamide 410.4 989

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[6-(4-methylpiperazin-1- yl)pyridin-3-yl]ethynyl}benzamide423.5 990

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]4-[(6-piperazin-1-ylpyridin-3- yl)ethynyl]benzamide 409.5 991

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(6-azepan-1-ylpyridin-3- yl)ethynyl]benzamide 422.5 992

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[6-(cyclobutylamino)pyridin-3- yl]ethynyl}benzamide 394.4993

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[6-(cyclohexylamino)pyridin-3- yl]ethynyl}benzamide 422.5994

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[6-(butylamino)pyridin-3- yl]ethynyl}benzamide 396.5 995

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(6-{[2-(methyloxy)ethyl]amino}pyridin-3- yl)ethynyl]benzamide 398.4 996

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4-{[4-(pipendin-1- ylmethyl)phenyl]ethynyl}benzamide 436.5 997

4-[(4-{[(2S)-2-amino-3-(4- aminophenyl)propanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 516.6998

4-((2S)-2-amino-3-{[4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)caxbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]amino}-3- oxopropyl)benzoic acid 545.6999

573.6 1000

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[1-(hydroxymethyl)-2-methylpropyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 497.6 1001

4-[4-(3-aminophenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)}benzamide 378.4 1002

4-[4-(3-{[(2-aminoethyl)amino]methyl}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide435.5 1003

5-[(4-{[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl)amino]-5-oxopentanoic acid453.5 1004

N-(2-aminoethyl)-3-{4-[4-({[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]buta-1,3- diynyl}benzamide 434.5 1005

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[3-(aminomethyl)phenyl]buta- 1,3-diynyl}benzamide 377.41006

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[3-(trifluoromethyl)phenyl]buta-1,3- diynyl}benzamide 416.4 1007

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-buta-1,3-diynylbenzamide 272.3 1008

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(2-methylphenyl)buta-1,3- diynyl]benzamide 362.4 1009

4-(4-{4-[(3-aminopropanoyl) amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide449.5 1010

4-[4-(3-{[(aminoacetyl)amino]methyl}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide449.5 1011

4-(4-{3-[(aminoacetyl)amino]phenyl)buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide435.4 1012

4-[4-(4-{[(2S)-2-aminopropanoyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide449.5 1013

4-(4-{4-[(aminoacetyl)amino]phenyl}buta-1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide420.4 1014

4-[4-(3-{[(aminoacetyl) amino]methyl}phenyl)buta-1,3-diynyl]-N-[(1S)-1-(aminomethyl)-2- (hydroxyamina)-2-oxoethyl]benzamide434.5 1015

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(3-aminopropanoyl)amino]phenyl}buta-1,3- diynyl)benzamide 434.5 1016

4-(4-{3-[(aminoacetyl)amino]phenyl}buta-1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide420.4 1017

4-[(4-{[(2S)-2-amino-3-(4-hydroxyphenyl)propanayl]amino}phenyl)ethynyl]- N-{(1S,2R)-2-hydroxy-1-[(hydxoxyamino)carbonyl]propyl}benzamide 517.6 1018

4-(4-{4-[(aminoacetyl)amino]phenyl)buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide435.4 1019

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(butylamino)methyl]phenyl}ethynyl)benzamide 409.5 1020

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-(piperidin-1- ylmethyl)phenyl]ethynyl}benzamide 421.51021

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-formylphenyl)ethynyl]benzamide 352.4 1022

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(methylsulfonyl)amino]phenyl}ethynyl)benzamide 432.5 1023

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(methylsulfonyl)amino]phenyl}ethynyl)benzamide 417.5 1024

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(phenylsulfonyl)amino]phenyl}ethynyl)benzamide 479.5 1025

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(phenylsulfonyl)amino]phenyl}buta-1,3- diynyl)benzamide 503.5 1026

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-(morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 423.51027

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(4-methylpiperazin-1-yl)methyl]phenyl}ethynyl)benzamide 436.5 1028

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-hydroxyethyl)amino]methyl}phenyl) ethynyl]benzamide 397.4 1029

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{(4-({[2-(methyloxy)ethyl]amino}methyl)phenyl]ethynyl}benzamide 411.5 1030

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(cyclohexylamino)methyl]phenyl}ethynyl) benzamide 435.5 1031

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(phenylmethyl)amino]methyl}phenyl)ethynyl]benzamide 443.5 1032

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(6-chloropyridin-3- yl)ethynyl]benzamide 359.8 1033

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[({[6-(methyloxy)pyridin-3- yl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 542.6 1034

4-{4-[4-({[(6-chloropyridin-3- yl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide547.0 1035

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(pyrrolidin-1- ylmethyl)phenyl]ethynyl}benzamide 422.5 1036

4-({4-[(ethylamino)methyl)phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 396.5 1037

4-({4-[(dimethylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)caxbonyl]propyl}benzamide 396.5 1038

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(4-methylpiperazin-1- yl)methyl]phenyl}ethynyl)benzamide 451.5 1039

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[3-(1H-imidazol-1-yl)propyl]amino}methyl)phenyl]ethynyl)benzamide 476.51040

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-thien-2-ylbuta-1,3- diynyl)benzamide 354.4 1041

N,N,N-triethyl-2-{[4-(4-{4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}buta-1,3-diynyl)phenyl]amino}-2-oxoethanaminium 520.6 1042

4-[4-(2-aminophenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)caxbonyl]propyl}benzamide 378.4 1043

4-[4-(3-{[(2-aminoethyl)amino]methyl}phenyl)buta-1,3-diynyl]-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide420.5 1044

4-buta-1,3-diynyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 287.3 1045

4-[4-(4-{[(2S)-2-amino-4- methylpentanoyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide491.6 1046

(2S)-N-[4-(4-{4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}buta-1,3-diynyl)phenyl]pyrrolidine-2-carboxamide 475.51047

(2S)-N-[4-(4-{4-[({(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl)buta-1,3-diynyl)phenyl]piperidine- 2-carboxamide 489.51048

4-[4-(4-{[(2S)-2,3- diaminopropanoyl]amino}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide464.5 1049

4-[4-(4-{[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino}phenyl)buta-1,3-diynyl]- N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 515.5 1050

N-[1-{(hydroxyamino)carbonyl]-2- (propylamino)propyl]-4-[(4-{[(propylamino)acetyl]amino}phenyl)ethynyl]benzamide 494.6 1051

4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]-N-{2-(cyclobutylamino)-1- [(hydroxyamino)carbonyl]propyl}benzamide 518.61052

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl)-4-[(4-{[(cyclopropylamino)acetyl]amino}phenyl) ethynyl]benzamide 450.5 1053

1-[(1R,2S)-2-[({4-[(4- {[(cyclopropylamino)acetyl]amino}phenyl)ethynyl]phenyl}carbonyl)amino]-3-(hydroxyamino)-1-methyl-3-oxopropyl]triaza-1,2-dien-2-ium 477.5 1054

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(4-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.61055

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}A-({4-[({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.61056

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl)propyl)-4-[(4-{[(propylamino)acetyl]amino}phenyl)ethynyl]benzamide 452.5 1057

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(phenylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 500.6 1058

1-((1R,2S)-3-(hydroxyamino)-1-methyl-3-oxo- 2-{[(4-{[4-({[(phenylmethyl)amino]acetyl}amino) phenyl]ethynyl}phenyl)carbonyl]amino}propyl)triaza- 1,2-dien-2-ium 527.6 1059

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl) ethynyl]benzamide 464.5 1060

1-[(1R,2S)-2-[({4-[(4- {[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]phenyl}carbonyl)amino]-3-(hydroxyamino)-1-methyl-3-oxopropyl]triaza- 1,2-dien-2-ium 491.5 1061

4-[(4-ethylphenyl)ethynyl]-N-{(1S)-1- [(hydroxyamino)carbonyl]-2-methylpropyl}benzamide 365.4 1062

4-(4-{4-[(ethylamino)methyl]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide420.5 1063

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(3-aminophenyl)buta-1,3- diynyl]benzamide 363.4 1064

4-(4-{3-[(4-aminobutanoyl)amino]phenyl)buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 463.5 1065

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(3-hydroxyphenyl)buta-1,3-diynyl]benzamide 379.4 1066

4-(4-{2-[(aminoacetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide435.4 1067

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[2,4-bis(methyloxy)pyrimidin-5-yl]buta-1,3-diynyl}benzamide 410.4 1068

(2S)-6-amino-2-{[(4-(4-{4-({[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]buta-1,3-diynyl}phenyl)carbonyl]amino}hexanoic acid 520.6 1069

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(2-aminophenyl)buta-1,3- diynyl]benzamide 363.4 1070

4-[4-(4-{2-[(2-aminoethyl)amino]-2-oxoethyl}phenyl)buta-1,3-diynyl]-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 448.5 1071

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-(2-aminopyrimidin-5-yl)buta- 1,3-diynyl]benzamide 365.41072

4-(4-{3-[(4-aminobutanoyl)aminolphenyl}buta-1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide 448.5 1073

4-(4-{2-[(aminoacetyl)amino]phenyl}buta-1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide420.4 1074

4-[4-(4-{2-[(2-aminoethyl)amino]-2-oxoethyl)phenyl)buta-1,3-diynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 463.5 1075

4-[4-(4-([(2,3- dihydroxypropyl)amino]methyl}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 466.5 1076

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4- [({[2-(methyloxy)phenyl]methyl}amino)methyl]phenyl}buta-1,3-diynyl)benzamide512.6 1077

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[(pyridin-2-ylamino)methyl]phenyl}buta-1,3- diynyl)benzamide 469.5 1078

4-[(4-{[(2-aminoethyl) amino]methyl}phenyl)buta-1,3-diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide435.5 1079

4-[(4-ethylphcnyl)ethynyl]-N-[(1R)-1-[(ethylthio)methyl]-2-(hydroxyamino)-2- oxoethyl]benzamide 397.5 1080

4-[(4-{[(2S)-2- aminopropanoyl]amino}phenyl)ethynyl]-N-[(1R)-1-[(ethylthio)methyl]-2-(hydxoxyamino)- 2-oxoethyl]benzamide 455.51081

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(3-chlorophenyl)buta-1,3- diynyl]benzamide 382.8 1082

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[3-(methyloxy)phenyl]buta-1,3- diynyl}benzamide 378.41083

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[(methylsulfonyl)amino]phenyl}buta-1,3- diynyl)benzamide 456.5 1084

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-(4-{3-[(methylsulfonyl)amino]phenyl}buta-1,3- diynyl)benzamide 456.5 1085

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-(4-pyrazin-2-ylbuta-1,3- diynyl)benzamide 350.3 1086

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(3-nitrophenyl)buta-1,3-diynyl]benzamide 408.4 1087

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(3-{[(methylsulfonyl)amino]methyl}phenyl) ethynyl]benzamide 446.5 1088

4-[(2-formylphenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 367.4 1089

N-{(1R,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(3-{[(methylsulfonyl)amino]methyl}phenyl) ethynyl]benzamide 446.5 1090

4-({2-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 411.4 1091

N-{(1S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[3-(morpholin-4-ylmethyl)phenyl]buta-1,3- diynyl}benzamide 462.5 1092

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(methylamino)methyl]phenyl}ethynyl) benzamide 367.4 1093

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(ethylamino)methyl]phenyl}ethynyl) benzamide 381.4 1094

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(propylamino)methyl]phenyl}ethynyl) benzamide 395.5 1095

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(pentylamino)methyl]phenyl)ethynyl)benzamode 423.5 1096

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{(4-[(hexylamino)methyl]phenyl}ethynyl)benzamide 437.6 1097

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(1-methylethyl)amino]methyl}phenyl) ethynyl]benzamide 395.5 1098

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2-methylpropyl)amino]methyl}phenyl) ethynyl]benzamide 409.5 1099

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(1,1-dimethylethyl)amino]methyl}phenyl) ethynyl]benzamide 409.5 1100

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(dimethylamino)methyl]phenyl}ethynyl)benzamide 381.4 1101

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[ethyl(methyl)amino]methyl}phenyl) ethynyl]benzamide 395.5 1102

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[2-oxoethyl]-4-{[4-({[2-(dimethylamino)ethyl]amino}methyl)phenyl]ethynyl}benzamide 424.5 1103

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[4-(dimethylamino)butyl]amino}methyl)phenyl]ethynyl}benzamide 452.6 1104

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2-cyanoethyl)amino]methyl}phenyl)ethynyl]benzamide 406.5 1105

4-{[4-({[2-(acetylamino) ethyl]amino}methyl)phenyl]ethynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 438.51106

4-[(4-{[(2- aminoethyl)amino]methyl}phenyl)ethynyl]-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 396.5 1107

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(3-hydroxypropyl)amino]methyl}phenyl)ethynyl]benzamide 411.5 1108

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[3-(methyloxy)propyl]amino}methyl)phenyl]ethynyl}benzamide 425.5 1109

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({methyl[2-(methyloxy)ethyl]amino}methyl)phenyl]ethynyl}benzamide 425.5 1110

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[3-(2-oxapyrrolidin-1-yl)propyl]amino}methyl)phenyl]ethynyl}benzamide 478.6 1111

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(3-morpholin-4-ylpropyl)amino]methyl}phenyl)ethynyl]benzamide 480.6 1112

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(cyclopropylamino)methyl]phenyl}ethynyl) benzamide 393.5 1113

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(cyclobutylamino)methyl]phenyl}ethynyl) benzamide 407.5 1114

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(cyclopentylamino)methyl]phenyl}ethynyl) benzamide 421.5 1115

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(cycloheptylamino)methyl]phenyl}ethynyl) benzamide 449.6 1116

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(cyclooctylamino)methyl]phenyl}ethynyl) benzamide 463.6 1117

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-(pyrrolidin-1- ylmethyl)phenyl]ethynyl)benzamide 407.51118

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-(azepan-1-ylmethyl)phenyl]ethynyl}benzamide 435.5 1119

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(3R)-3-(dimethylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]benzamide 450.61120

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(3S)-3-(dimethylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]benzamide 450.61121

4-[(4-{[(3R)-3-(acetylamino)pyrrolidin-1-yl]methyl}phenyl)ethynyl]-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide 464.5 1122

4-[(4-{[(3S)-3-(acetylamino)pyrrolidin-1-yl]methyl}phenyl)ethynyl]-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide 464.5 1123

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-(1,4′-bipipendin-1′- ylmethyl)phenyl]ethynyl}benzamide504.6 1124

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(cyclohexylmethyl)amino]methyl}phenyl) ethynyl]benzamide 449.6 1125

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[cyclohexyl(methyl)amino]methyl}phenyl) ethynyl]benzamide 449.6 1126

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1R)-1-phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1127

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1S)-1-phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1128

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(thien-2-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 449.5 1129

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2-phenylethyl)amino]methyl}phenyl)ethynyl]benzamide 457.5 1130

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(piperidin-3- ylamino)methyl]phenyl}ethynyl)benzamide436.5 1131

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(piperidin-4- ylamino)methyl]phenyl}ethynyl)benzamide436.5 1132

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(piperidin-2-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 450.6 1133

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(piperidin-3-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 450.6 1134

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2R)-pyrrolidin-2-ylmethyl]amino}methyl)phenyl]ethynyl}benzamide 436.5 1135

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(2S)-pyrrolidin-2-ylmethyl]amino}methyl)phenyl]ethynyl}benzamide 436.5 1136

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(pyrrolidin-3- ylamino)methyl]phenyl}ethynyl)benzamide422.5 1137

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2-fluorophenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 461.5 1138

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-([4-({[(3-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 461.5 1139

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(4-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 461.5 1140

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1141

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(3-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1142

N-[(1S)-1-(aninomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{(4-({[(4-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1143

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[2-(methyloxy)phenyl]methyl}amino)methyl]phenyl}ethynyl)benzamide 473.51144

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[3-(methyloxy)phenyl]methyl}amino)methyl]phenyl}ethynyl)benzamide 473.51145

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[4-(methyloxy)phenyl]methyl}amino)methyl]phenyl}ethynyl)benzamide 473.51146

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(phenylamino)methyl]phenyl}ethynyl) benzamide 429.5 1147

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-3-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 444.5 1148

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(4-phenylpiperidin-1-yl)methyl]phenyl}ethynyl)benzamide 497.6 1149

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[(4-phenylpiperazin-1-yl)methyl]phenyl}ethynyl)benzamide 498.6 1150

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(1R,2R,4S)- bicyclo[2.2.1]hept-2-ylamino]methyl}phenyl)ethynyl]benzamide 447.5 1151

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({[(1S,2R,5S)-6,6- dimethylbicyclo[3.1.1]hept-2-yl]methyl}amino)methyl]phenyl}ethynyl) benzamide 489.6 1152

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(1S,4R)-bicyclo[2.2.1]hept-2-ylamino]methyl}phenyl)ethynyl]benzamide 447.5 1153

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[(1S,2S,3S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept-3-yl]amino}methyl)phenyl]ethynyl}benzamide 489.6 1154

1-((1R,2S)-3-(hydroxyamino)-1-methyl-3-oxo- 2-{[(4-{(4-({[(pyridin-4-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}phenyl)carbonyl]amino}propyl)triaza-1,2-dien-2-ium 528.6 1155

1-((1R,2S)-3-(hydroxyamino)-1-methyl-3-oxo- 2-{[(4-{[4-({[(pyridin-3-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}phenyl)carbonyl]amino}propyl)triaza-1,2-dien-2-ium 528.6 1156

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(pyridin-4- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzmide 501.61157

N-{(1S,2R)-2-amino-1- [(hydroxyamino)caxbonyl]propyl}-4-{[4-({[(pyridin-3- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide501.6 1158

N-[1-[(hydroxyamino)carbonyl}-2- (methylamino)propyl]-4-{[4-({[(phenylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 514.6 1159

4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]-N-[1-[(hydroxyamino)carbonyl]-2- (methylamino)propyl]benzamide478.6 1160

4-[(4-{[(2S)-2- aminopropanoyl]amino}phenyl)ethynyl]-N-[(1R)-1-{[ethyl(hydroxy)-lambda˜4˜- sulfanyl]methyl}-2-(hydroxyamino)-2-oxoethyl]benzamide 473.6 1161

4-[(4-ethylphenyl)ethynyl]-N- hydroxybenzamide 266.3 1162

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(2,4-difluorophenyl)buta-1,3- diynyl]benzamide 384.4 1163

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(2-aminophenyl)ethyuyl]benzamide 339.4 1164

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(3-{[(methylsulfonyl)amino]methyl}phenyl)buta- 1,3-diynyl]benzamide 455.51165

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(3-{[(methylsulfonyl)amino]methyl}phenyl)buta- 1,3-diynyl]benzamide 455.51166

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({3-[(methylsulfonyl)amino]phenyl}ethynyl) benzamide 417.5 1167

4-[(4-{[(2S)-2- aminopropanoyl]amino}phenyl)ethynyl]-N- hydroxybenzamide324.4 1168

4-[(2-{[(2-aminoethyl)amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}benzamide 411.51169

N-{(1R,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-(phenylethynyl)benzamide 338.4 1170

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4-aminophenyl)buta-1,3-diynyl]benzamide 377.4 1171

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(3-hydroxyphenyl)buta-1,3- diynyl]benzamide 364.4 1172

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-f3-(morpholin-4- ylmethyl)phenyl]buta-1,3-diynyl)benzamide 447.5 1173

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[2-(methyloxy)phenyl]methyl}amino)methyl]phenyl}ethynyl)benzamide 488.61174

4-[(4-{[(2,3- dihydroxypropyl)amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}benzamide 442.51175

4-({2-[(dimethylamino) methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 396.5 1176

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(methylamino)methyl]phenyl}ethynyl)benzamide 382.4 1177

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(propylamino)methyl]phenyl}ethynyl)benzamide 410.5 1178

4-({4-[(butylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 424.5 1179

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(pentylamino)methyl]phenyl}ethynyl)benzamide 438.5 1180

4-({4-[(hexylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 452.6 1181

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(1-methylethyl)anuinojmethyl}phenyl)ethynyl]benzamide 410.5 1182

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(2-methylpropyl)amino]methyl}phenyl)ethynyl]benzamide 424.5 1183

4-[(4-{[(1,1- dimethylethyl)amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 424.51184

4-[(4-{[ethyl(methyl) amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)benzamide 410.51185

4-{[4-({[2-(dimethylamino)ethyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 439.5 1186

4-{[4-({[4-(dimethylamino)butyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 467.6 1187

4-[(4-{[(2- hydroxyethyl)amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 412.51188

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(3-hydroxypropyl)amino]methyl}phenyl) ethynyl]benzamide 426.5 1189

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbanyl]propyl}-4-{[4-({methyl[2- (methyloxy)ethyl]amino}methyl)phenyl]ethynyl}benzamide 440.51190

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[2-(methyloxy)ethyl]amino}methyl)phenyl]ethynyl}benzamide 426.5 1191

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[3-(methyloxy)propyl]amino)methyl)phenyl]ethynyl}benzamide 440.5 1192

4-[(4-{[(2- cyanoethyl)amino]methyl}pheny-ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 421.51193

4-{[4-({[2-(acetylamino)ethyl]aznmo}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 453.5 1194

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[3-(2-oxopyrrolidin-1- yl)propyl]amino}methyl)phenyl]ethynyl}benzamide493.6 1195

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(3-morpholin-4-ylpropyl)amino]methyl}phenyl)ethynyl]benzamide 495.6 1196

4-({4-[(cyclopropylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 408.5 1197

4-({4-[(cyclobutylamino)methyl]phenyl}ethynyl)-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl)benzamide 422.5 1198

4-({4-[(cyclopentylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 436.5 1199

4-({4-[(cyclohexylamino)methyl]phenyl)ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 450.5 1200

4-({4-[(cycloheptylamino)xnethyl]phenyl)ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.61201

4-({4-[(cyclooctylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)caxbonyl]propyl)benzamide 478.6 1202

4-{[4-(azepan-1-ylmethyl)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 450.5 1203

4-[(4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 465.6 1204

4-[(4-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 465.6 1205

4-[(4-{[(3R)-3-(acetylamino)pyrrolidin-1-yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 479.5 1206

4-[(4-{[(3S)-3-(acetylamino)pyrrolidin-1-yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 479.5 1207

4-{[4-(1,4′-bipiperidin-1′- ylmethyl)phenyl]ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 519.7 1208

4-[(4- {[(cyclobexylmethyl)amino]methyl}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 464.6 1209

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(4-phenylpiperazin-1- yl)methyl]phenyl}ethynyl)benzamide 513.6 1210

N-{(1S,2R)-2-hydxoxy-1- [(hydroxyamino)caxbonyl]propyl}-4-{(4-{[(2-phenylethyl)amino]methyl}phenyl)ethynyl]benzamide 472.6 1211

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{(4-({[(1R)-1- phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1212

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(1S)-1- phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1213

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(thie-2- ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 464.6 1214

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(piperidin-3- ylamino)methyl]phenyl}ethynyl)benzamide 451.5 1215

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(piperidin-4- ylamino)methyl]phenyl}ethynyl)benzamide 451.5 1216

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(piperidin-2- ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 465.61217

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[(piperidin-3- ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 465.61218

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2R)-pyrrolidin-2- ylmethyl]amino}methyl)phenyl]ethynyl}benzamide451.5 1219

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-([4-({[(2S)-pyrrolidin-2- ylmethyl]amino}methyl)phenyl]ethynyl}benzamide451.5 1220

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(pyrrolidin-3- ylamino)methyl]phenyl}ethynyl)benzamide 437.5 1221

4-{[4-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 476.5 1222

4-{[4-({[(3-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 476.5 1223

4-{[4-({[(4-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 476.5 1224

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(2-methylphenyl)methyl]amino}methyl)phenyl]ethynyl)benzamide 472.6 1225

N-{(1S,2R)-2-hydroxy-1- [(hydxoxyamino)carbonyl]propyl}-4-([4-({[(3-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1226

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(4-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1227

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl)-4-[(4-{[(phenylmethyl)amino]methyl}phenyl) ethynyl]benzamide 458.5 1228

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(phenylamino)methyl]phenyl}ethynyl) benzamide 444.5 1229

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[-pyridin-3-ylmethyl) amino]methyl}phenyl)ethynyl]benzamide 459.5 1230

4-[(4-{[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]methyl}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 462.6 1231

(3R)-N-hydroxy-3-({[4- (phenylethynyl)phenyl]carbonyl}amino)piperidine-3-carboxamide 364.4 1232

4-({[4-(phenylethynyl)phenyl]carbonyl)amino)piperidine-4-carboxylic acid349.4 1233

N-{(1S)-2-(hydroxyamino)-2-oxo-1-[(2S)- pyrrolidin-2-ylmethyl]ethyl}-4-(phenylethynyl)benzamide 378.4 1234

(3R)-3-{[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]amino}-N-hydroxypiperidine-3- carboxamide 368.4 1235

1,1-dimethylethyl 3-(4-{4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}buta-1,3-diynyl)phenylcarbamate 478.5 1236

4-[4-(3-amino-4-methylphenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 392.4 1237

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(3-amino-4-methylphenyl) buta-1,3-diynyl]benzamide 377.41238

4-(4-{4-[(aminoacetyl)anxmo]-3- methylphenyl}buta-1,3-diynyl)-N-[(1S)-1-(aminomediyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 434.5 1239

N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-(2-phenylethenyl)benzamide 340.4 1240

N-[(2R)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4′-ethyl-1,1′-biphenyl-4-carboxamide 328.4 1241

N-[(2R)-2-amino-3-(hydroxyamino)-3-oxopropyl]-4-(phenylethynyl)benzamide 324.4 1242

N-[(2R)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4-(4-chlorophenyl)cyclohexanecarboxamide 340.8 1243

N-[(2S)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4-(4-chlorophenyl)cyclohexanecarboxamide 340.8 1244

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[2-(4-methylphenyl)ethyl]benzamide 342.4 1245

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-aminophenyl)butyl]benzamide 371.4 1246

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4-{[4-({[methyl(pyridin-2-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 516.6 1247

4-{[4-({[[(2-fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}berazamide 533.6 1248

4-{[4-({[[(3-fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 533.6 1249

4-{[4-({[[(4-fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 533.6 1250

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[(2-fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide518.6 1251

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[(3-fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide518.6 1252

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[(4-fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide518.6 1253

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({methyl[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 514.61254

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-({4-[({methyl[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 514.61255

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(phenylmethyl)amino]acetyl}amino) phenyl]ethynyl}bexizamide500.6 1256

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[methyl(propyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 467.5 1257

4-{[4-({[butyl(methyl)amino]acetyl)amino)phenyl]eyhynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 481.61258

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[methyl(pentyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 495.6 1259

5-{[4-({[hexyl(methyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 509.6 1260

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[methyl(1-methylethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide467.5 1261

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[methyl(2- methylpropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide481.6 1262

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({methyl[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 529.61263

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({methyl[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 529.61264

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(propyl)amino]acetyl}amino) phenyl]ethynyl)benzamide 452.5 1265

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[butyl(methyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 466.6 1266

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(pentyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 480.6 1267

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[hexyl(methyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 494.6 1268

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(1-methylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 452.5 1269

N-{(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(2-methylpropyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 466.6 1270

N-[(1S)-1-(aminomethyl)-2-(hyddroxyamino)-2-oxoethyl]-4-{[4-({[methyl(pyridin-2-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 501.6 1271

4-{[4-({[(3,4-dihydroxyphenyl)methyl]amino}methyl)phenyl]ethynyl)-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 490.5 1272

4-({2-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2S)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 411.4 1273

4-[(4-{[(2S)-2- aminopropanoyl]amino}phenyl)ethynyl]-N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 425.51274

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-(diethylamino)phenyl]ethynyl}benzamide 395.5 1275

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-{ethylamino)phenyl]buta- 1,3-diynyl}benzamide 391.41276

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[(4-{[(2-amino-2-oxoethyl)amino]methyl}phenyl)ethynyl]benzamide 410.4 1277

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{[4-({[1-(hydroxymethyl)-2-methylpropyl]amino}methyl)phenyl]ethynyl)benzamide 439.5 1278

N-[(1S)-1-(aminomethyl)-2-(hydxoxyamino)-2- oxoethyl]-4-({4-[(pyridin-2-ylamino)methyl]phenyl}ethynyl)benzamide 430.5 1279

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[3-(ethylamino)phenyl]buta- 1,3-diynyl}benzamide 391.41280

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3-(ethylamino)phenyl]ethynyl}benzamide 367.4 1281

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-(hydroxymethyl)phenyl]ethynyl}benzamide 354.4 1282

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3-(diethylamino)phenyl]ethynyl}benzamide 395.5 1283

N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-(morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 438.5 1284

4-({4-[(dimethylamino)methyl]phenyl}ethynyl)-N- {(1S,2S)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 396.5 1285

4-[(4-aminophenyl)ethynyl]-N-{(1S,2S)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 354.4 1286

4-[4-(4-aminophenyl)buta-1,3-diynyl]-N- {(1S,2S)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 378.4 1287

1,1-dimethylethyl 4-(4-{4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}buta-1,3-diynyl)phenylcarbamate 478.5 1288

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-({[1-(hydroxymethyl)-2-methylpropyl]amino)methyl)phenyl]buta-1,3- diynyl}benzamide 463.5 1289

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(4-hydroxyphenyl)buta-1,3- diynyl]benzamide 364.4 1290

4-[(2,4-difluorophenyl)ethynyl]-N-{(1S,2S)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 375.3 1291

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-{4-[4-(morpholin-4-ylmethyl)phenyl]buta-1,3-diynyl}benzamide 447.5 1292

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-(hydroxymethyl)phenyl]buta-1,3- diynyl}beazaxriide 378.4 1293

4-({3-[(2-aminoethyl)amino]phenyl}ethynyl)- N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 397.4 1294

N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-(trifluoromethyl)phenyl]ethynyl}benzamide 392.3 1295

(2S,3R)-3-hydroxy-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)butanoicacid 324.3 1296

N-((1S,2R)-1-{[(2- aminoethyl)amino]carbonyl}-2-hydroxypropyl)-4-(phenylethynyl)benzamide 366.4 1297

1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-({[4-(4-phenylbuta-1,3-diynyl)phenyl]carbonyl}amino) propylcarbamate 448.5 1298

N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl)-4-(4-{4-[(3-morpholin-4-ylpropyl)amino]phenyl}buta-1,3- diynyl)benzamide 505.6 1299

N-[(1S,2R)-2-hydroxy-1-({[2- (methylthio)phenyl]amino}carbonyl)propyl]-4-(phenylethynyl)benzamide 445.6 1300

N-{(1S,2R)-2-hydroxy-1-[(pyridin-2- ylamino)carbonyl]propyl}-4-(phenylethynyl)benzamide 400.4 1301

N-((1S)-1-(aminomethyl)-2-{[(1,1-dimethylethyl)oxy]amino}-2-oxoethyl)-4-(4-phenylbuta-1,3-diynyl)benzamide 404.5 1302

N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}-4-(4-phenylbuta-1,3-diynyl)benzamide 363.4 1303

(2S,3R)-N,3-dihydroxy-2-({[4-(4-phenylbuta-1,3-diynyl)phenyl]methyl}amino)butanamide 349.4 1304

1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-({[4-(4-phenylbuta-1,3-diynyl)phenyl]methyl}amino)propylcarbamate 434.5 1305

(2S)-3-amino-N-hydroxy-2-({[4-(4-phenylbuta-1,3-diynyl)phenyl]methyl}amino)propanamide 334.4 1306

N-[(1S)-2-(hydroxyamino)-1-(hydroxymethyl)- 2-oxoethyl]-4-[(trifluoromethyl)oxy]benzamide 309.2 1307

N-{2-hydroxy-1-[(hydroxyamino)carbonyl]-2- phenylethyl}-4-[(trifluoromethyl)oxy]benzamide 385.3

1.-24. (canceled)
 25. A compound according to Formula (I)

R⁴ and R are selected from the group consisting of H, F, lower alkyl,CF₃, CH₂═CHCH₂O—, MeO—, and CF₃O—; and AA is an amino acid residueselected from the group consisting of L-Ser, L-Thr, and L-allo-Thr. 26.A compound according to Formula (II)

AA is an amino acid residue selected from the group consisting of L-Thr,L-allo-Thr, and L-Val; R is H or CH₃O—; G is absent, —CH═CH—, —C≡C—,

 or —C≡C—C≡C— and Y is substituted or unsubstituted aryl or heteroaryl.27. The compound of claim 26, wherein AA is L-Thr.
 28. The compound ofclaim 26, wherein AA is L-allo-Thr.
 29. The compound of claim 26,wherein G is —C≡C—.
 30. The compound of claim 26, wherein G is —CH═CH—.31. The compound of claim 26, wherein Z is CH₂ and G is —C≡C—C≡C—. 32.The compound of claim 26, wherein G is —C≡C—C≡C— or —C═C— and Y is asubstituted or unsubstituted heteroaryl.
 33. A compound according toFormula (III)

wherein: R is H or MeO; AA is an amino acid residue selected from thegroup consisting of L-Thr, L-allo-Thr, and L-Val; R¹ and R⁴ areindependently H, CH₃, CF₃, CH₃CH₂—, F—, HO—, MeO—, CF₃O—, H₂N—,Me₂NCH₂—, (AA)¹-NH—, (AA)¹-NHCH₂—, R³NHCH₂—, R^(3′)NHCO—, R^(3′)NHCOCH₂—or R^(3′)NHCOCH₂O—,

R³ is H, lower alkyl, or aminoalkyl; R^(3′) is lower alkyl oraminoalkyl; and (AA)¹ is an amino acid or dipeptide, n=1 or
 2. 34. Thecompound of claim 33, wherein AA is L-Thr.
 35. The compound of claim 33,wherein AA is L-allo-Thr.
 36. The compound of claim 33, wherein R¹ or R⁴is (AA)¹-NH—.
 37. The compound of claim 33, wherein R¹ or R⁴ is(AA)¹-NHCH₂—.
 38. The compound of claim 33, wherein R¹ or R⁴ is


39. The compound of claim 33, wherein R¹ or R⁴ is


40. The compounds of claim 33, wherein R¹ or R⁴ is

and AA is L-Thr or L-allo-Thr.
 41. A compound according to Formula (III)

wherein: AA is L-Dap; R=H or F; R⁴ is selected from the group consistingof CH₃CH₂—, H₂N—, Et₂N—, HOCH₂—, CF₃—, CF₃O—, H₂N—CH₂—CO—NH—, R³NHCOCH₂—and R³NHCOCH₂O—; and R³ is lower alkyl, hydroxyalkyl, aminoalkyl, orhydroxy.
 42. A compound according to Formula (IV)

wherein: AA=L-Thr or L-Dap; R⁴ is selected from the group consisting ofHONHCO—CH(CHMeOH)—NH—CO, HONHCO—CH(CH₂NH₂)—NH—CO—, (AA)¹-NH—CO—, HO—,HOCH₂—, H₂N—CH₂—CONH—, R″NH—, or R″NHCH₂;

R″=Et, hydroxyalkyl or H₂N(CH₂)₂—; (AA)¹ is any amino acid; n is 0-1;and m is 1-3.
 43. The compounds of claim 42, wherein R⁴ is


44. The compounds of claim 42, wherein R⁴ is H₂N—CH₂—CONH—.
 45. Thecompounds of claim 42, wherein R⁴ is


46. The compounds of claim 42, wherein R⁴ is HOCH₂—.
 47. A compoundaccording to Formula (IV)

wherein: AA L-Thr or L-Dap; R⁴=H or CH₃; R² and R³ are independentlyselected from the group consisting of H, CH₃—, H₂N—, EtNH—, HO—, Cl—,CF₃—,

 H₂NCH₂CH₂NHCH₂—,  NH₂—CH₂—,  —RNH—CH₂—,

R=aminoalkyl; and (AA)¹ is any amino acid, with the proviso that R² andR³ are not both H.
 48. The compound of claim 47, wherein R³ is HO—. 49.The compound of claim 47, wherein R³ is H₂N—.
 50. The compound of claim47, wherein R³ is


51. The compound of claim 47, wherein R³ is AA¹-H— in the form ofH₂N—CH₂—CONH—.
 52. The compound of claim 47, wherein R³ is AA¹-NH—CH₂—in the form of H₂N—CH₂—CONHCH₂—.
 53. The compound of claim 47, whereinR³ is H₂N—CH₂CH₂—NHCH₂—.
 54. The compound of claim 47, wherein R³ isNH₂—CH₂—.
 55. A pharmaceutical composition comprising: the compoundaccording to claim 25 and a pharmaceutically acceptable excipient.
 56. Apharmaceutical composition comprising: the compound according to claim26 and a pharmaceutically acceptable excipient.
 57. A pharmaceuticalcomposition comprising: the compound according to claim 33 and apharmaceutically acceptable excipient.
 58. A pharmaceutical compositioncomprising: the compound according to claim 41 and a pharmaceuticallyacceptable excipient.
 59. A pharmaceutical composition comprising: thecompound according to claim 42 and a pharmaceutically acceptableexcipient.
 60. A pharmaceutical composition comprising: the compoundaccording to claim 47 and a pharmaceutically acceptable excipient.
 61. Amethod of treating infection in a subject comprising: administering aneffective amount of the compound according to claim 25 to the subject.62. A method of treating infection in a subject comprising:administering an effective amount of the compound according to claim 26to the subject.
 63. A method of treating infection in a subjectcomprising: administering an effective amount of the compound accordingto claim 33 to the subject.
 64. A method of treating infection in asubject comprising: administering an effective amount of the compoundaccording to claim 41 to the subject.
 65. A method of treating infectionin a subject comprising: administering an effective amount of thecompound according to claim 42 to the subject.
 66. A method of treatinginfection in a subject comprising: administering an effective amount ofthe compound according to claim 47 to the subject.